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Autoimmune encephalitis is a relatively novel nosological entity characterized by an immune-mediated damage of the central nervous system. While originally described as a paraneoplastic inflammatory phenomenon affecting limbic structures, numerous instances of non-paraneoplastic pathogenesis, as well as extra-limbic involvement, have been characterized. Given the wide spectrum of insidious clinical presentations ranging from cognitive impairment to psychiatric symptoms or seizures, it is crucial to raise awareness about this disease category. In fact, an early diagnosis can be dramatically beneficial for the prognosis both to achieve an early therapeutic intervention and to detect a potential underlying malignancy. In this scenario, the radiologist can be the first to pose the hypothesis of autoimmune encephalitis and refer the patient to a comprehensive diagnostic work-up - including clinical, serological, and neurophysiological assessments.In this article, we illustrate the main radiological characteristics of autoimmune encephalitis and its subtypes, including the typical limbic presentation, the features of extra-limbic involvement, and also peculiar imaging findings. In addition, we review the most relevant alternative diagnoses that should be considered, ranging from other encephalitides to neoplasms, vascular conditions, and post-seizure alterations. Finally, we discuss the most appropriate imaging diagnostic work-up, also proposing a suggested MRI protocol. more...

Background: The interpretation of antibodies to glutamic acid decarboxylase 65 (GAD-Abs) in neurological practice is challenging. GAD-Abs are not considered directly pathogenic and immunotherapy guidelines are lacking. Methods: We undertook a single-center retrospective service evaluation of GAD-Abs, documenting clinical features, immunotherapy responses, and outcomes of 335 patients with positive GAD-Abs measured by indirect ELISA between 2012 and 2020. The serum:CSF ratio of GAD-Ab values was used as a surrogate for intrathecal synthesis. Results: 168 (50%) patients had diagnosed neurological disorders (GAD-ND). Ninety-six had neurological disorders often or sometimes associated with GAD-Abs, i.e., stiff person syndrome spectrum disorders (SPS-SD, n = 26), cerebellar ataxia (n = 21), epilepsy (n = 19), encephalitis (n = 18), or any combination of these (“mixed”, n = 12). Seventy-two had other neurological disorders (ONDs) not typically associated with GAD-Abs. We defined a cut-off of 10,000 IU/mL a priori and a posteriori for GAD-Ab associated NDs, but identified values > 10,000 IU/mL in 21% and 11% of patients with ONDs or diabetes respectively, and < 10,000 IU/mL in 39% patients with classical GAD-Ab syndromes, indicating low assay specificity and sensitivity. Low serum: CSF GAD-Ab ratios were consistent with intrathecal synthesis in 12/19 tested; 25/54 patients had oligoclonal bands. 30/50 patients given adequate immunotherapies had partial (n = 17) or good (n = 13) responses, particularly those with SPS-SD or limbic encephalitis. Within the limitations of small subgroups and routine laboratory titrations, patients with GAD-Ab values > 10,000 IU/mL, intrathecal synthesis of GAD-Abs, or oligoclonal bands, were not more likely to improve with immunotherapies than those with GAD-Ab values < 10,000 IU/mL and a non-inflammatory CSF. Rather, treatment response correlated with disease group, principally SPS-SD and encephalitis. Conclusions: These results suggest caution in over-interpreting GAD-Abs values. Better biomarkers for identifying patients with immunotherapy responsive GAD-Ab disease are needed. [ABSTRACT FROM AUTHOR] more...

Limbic encephalitis is a disease included in the group of autoimmune encephalitis triggered by different factors, including paraneoplastic, infectious, and pharmacological, among others. The main symptoms are memory impairment, seizures, and psychiatric symptoms. This disease can cause severe neuropsychiatric and cognitive sequelae if not treated in a timely manner, and, if underdiagnosed, it can worsen the prognosis when an underlying unidentified tumor exists. Given the importance of this condition, we wrote this article to provide an update on the diagnostic and therapeutic approach for these patients, according to possible findings in imaging, serum, and cerebrospinal fluid studies. Antibody detection tests can be used to identify, according to the location of the antigen (cellular surface, intracelular or synaptic), the relationship with tumors, response to treatment and prognosis. In case of paraneoplastic encephalitis, the therapeutic approach includes specific oncological treatment, immunotherapy, and symptom management, generally simultaneously. more...

Background and objective: Despite constituting one-third of suspected autoimmune encephalitis (AE) patients, antibody-negative cases without typical AE features are understudied. We aim to characterize the clinical phenotypes and long-term outcomes of "possible only" and "probable" AE cases. Methods: We conducted a retrospective analysis of adult patients evaluated at Mayo Clinic's Autoimmune Neurology Clinic (01/01/2006–12/31/2020), meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with ≥ 1 year of follow-up. All patients underwent neural antibody testing. Results: Among fifty-one patients, six had a change in diagnosis (non-autoimmune, 2) and were excluded from further analysis. Forty-five patients were analyzed [median age, 61 years (range 20–88); female, 21 (47%); median follow-up, 36 months (range 12–174)]. A nadir modified Rankin Scale (mRS) ≥ 3 was recorded in 41/45 (91%). CSF was inflammatory in 20/44 (45%) and MRI had encephalitic changes in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two patients (4%) had paraneoplastic causation. Relapses (> 3 months from onset) were noted in 14 (31%). Memory dysfunction (69%), attention deficits (38%), and gait instability (29%) were the most frequent at the last follow-up. Most patients (76%) were independent at the last follow-up and only two required an assistive device to ambulate; 11 patients (24%) had poor neurological outcome (mRS ≥ 3). Higher mRS score and gait assistance requirement at 3 months were predictive of poor outcome (P ≤ 0.01). Discussion: Despite significant disability at initial disease stages, most antibody-negative AE patients regain independent functioning. Early functional status and gait assistance requirements may predict long-term prognosis. [ABSTRACT FROM AUTHOR] more...

Objectives: neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease mainly affecting optic nerves and the spinal cord. Due to the potentially irreversible tissue damage, prevention of relapses is of utmost importance. Methods: We describe the atypical clinical course and pathology results of a patient with anti-aquaporin-4 antibody (anti-AQP4-Ab)-associated NMOSD who developed aseptic meningitis followed by limbic-encephalitis-like presentation with extensive brain lesions upon treatment with rituximab and tocilizumab. Results: The patient developed subacute cognitive decline with magnetic resonance imaging (MRI) evidence of extensive brain white matter lesions. In the hypothesis of an opportunistic brain infection, she underwent brain biopsy of the temporal pole. Pathology results revealed typical NMOSD findings with complement activation, supporting the hypothesis of an atypical presentation of anti-AQP-Ab-associated NMOSD. Accordingly, treatment with the complement-targeting drug eculizumab was started, leading to a dramatic clinical and MRI improvement. Discussion: aseptic meningitis and limbic encephalitis could represent a rare phenotype of anti-AQP4-Ab-associated NMOSD. [ABSTRACT FROM AUTHOR] more...

Temporal and parahippocampal glial tumors at early morphological stages of their development may mimic the clinical and neuroimaging picture of limbic encephalitis. Delayed diagnosis of glioblastoma can have a negative impact on the prognosis of the disease, which is why there is a need to find approaches for its earlier detection. The aim of this paper is to analyze possible difficulties and errors in the differential diagnosis of autoimmune encephalitis (AE) and glioblastoma based on literature data and our own clinical observations. Features such as onset of the disease at a young age, subacute development of symptoms, response to immunosuppressive therapy and the MRI imaging of bilateral T2 hyperintense changes in the limbic areas are typical for AE, but do not exclude the diagnosis of a primary tumor of the central nervous system. Therefore, caution should be exercised regarding the likelihood of a primary brain tumor when patients of any age group present with symptoms characteristic of AE, especially if no specific for AE antibodies are detected. To shorten the time to diagnosis, a multidisciplinary approach, critical analysis of clinical data, a shortening of the examination interval and an increase in the frequency of imaging follow-up examinations are required. more...

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. more...

Paraneoplastic limbic encephalitis is a rare condition reported in practice. It is most commonly associated with small cell lung cancer (SCLC). This case report is offered to aid physicians in making informed decisions about timing and type of treatment and is evident, that quick diagnosis is critical for both, neurologists and oncologists. The presentation reviews the case of a female patient diagnosed with limbic encephalitis. Further research is needed to establish clinical, laboratory and instrumental criteria that may be related to outcomes. The purpose of this paper is to present the potential repercussions of a delayed diagnosis and highlight the beneficial results of specific investigations and symptomatic therapy. Comprehensive familiarity with clinical presentations and the limitations of current diagnostic procedures is imperative for neurologists. Equally essential is this understanding for radiologists, serving as the basis for accurate diagnostic analyses derived from imaging findings. The intricate nature of neurological disorders sometimes necessitates the cooperation of neurologists, radiologists, and, in this particular instance, oncologists, in order to achieve precise diagnosis and develop successful treatment approaches. [ABSTRACT FROM AUTHOR] more...

Purkinje cell cytoplasmic antibody type 2 (PCA-2), identified in 2000, targets the widely distributed microtubule-associated protein 1B in the central and peripheral nervous systems, leading to diverse clinical phenotypes of neurological disorders. We report two cases of PCA-2-associated encephalitis, each presenting with distinct onset forms and clinical manifestations, thereby illustrating the phenotypic variability of PCA-2- related diseases. The first patient was diagnosed with PCA-2-associated autoimmune cerebellitis and undifferentiated small cell carcinoma with metastasis in mediastinal lymph nodes of unknown primary origin. The second patient was diagnosed with PCA-2-associated limbic encephalitis. Our findings underscore the superior sensitivity of positron emission tomography-computed tomography over brain magnetic resonance imaging in the early detection of PCA-2-associated encephalitis. Given the high risk of relapse and suboptimal response to traditional immunotherapy in PCA-2-related neurological disorders, this study highlights the need for a deeper understanding of their pathogenesis to develop more effective treatments to control symptoms and improve patient prognosis. [ABSTRACT FROM AUTHOR] more...

Background: Autoimmune limbic encephalitis (ALE) is a rare inflammatory disorder characterised by a subacute onset, usually within weeks. The presence of multiple neuropsychiatric symptoms such as seizures, short-term memory deficits, anxiety and depression often leads to misdiagnosis as another medical condition, contributing to poor prognosis and reduced long-term survival. Case description: A 60-year-old man, with no chronic illnesses, presented at the emergency department with daily episodes of palpitations, shivering, piloerection and a sense of impending doom lasting two months. Initially diagnosed with anxiety disorder and treated with venlafaxine 50 mg daily, he showed no improvement and developed memory loss. Hospitalised three months later, he exhibited both temporal and spatial disorientation, along with short-term memory loss. Key findings included elevated serum sedimentation rate, hyponatraemia, increased cerebrospinal fluid (CSF) protein levels and cranial magnetic resonance imaging evidence of bilateral temporal intra-parenchymal lesions, suggesting limbic encephalitis. After ruling out alternative diagnoses, screening of autoantibodies in the CSF was requested, which was positive for anti-LGI1 antibodies. The diagnosis of anti-LGI1 ALE was assumed, and treatment was initiated with significant clinical and imaging improvement. Conclusions: ALE’s broad clinical spectrum contributes to underdiagnosis. Therefore, in patients with new onset of neuropsychiatric symptoms and no prior psychiatric history, ALE should be considered, as prompt diagnosis and treatment are pivotal to achieve a good prognosis. more...

Background and objectivesLimbic predominant age-related TAR DNA binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC) is a prevalent degenerative pathology in the oldest-old who are the fastest-growing segment of our population with the highest rates of dementia. We aimed to determine the relationship between LATE-NC and cognitive impairment and to identify its potential risk factors by studying its relationship with common past medical histories in an oldest-old cohort.MethodsParticipants from The 90+ Study with longitudinal evaluations and autopsy data were included. Dementia status and impairment in 5 main cognitive domains were determined at postmortem conferences leveraging all clinical and neuropsychological data blind to neuropathologic diagnosis. Medical history information was obtained from patients and their informants. LATE-NC and Alzheimer disease neuropathologic change (ADNC) were considered present in those with TDP-43 pathology in the hippocampus and/or neocortex and those with high likelihood of ADNC according to NIA-AA guidelines, respectively. We examined the association of degenerative pathologies with cognitive outcomes and multiple comparisons-adjusted relationship of medical history variables with LATE-NC and ADNC using logistic regressions adjusted for age at death, sex, and education.ResultsThree hundred twenty-eight participants were included in this study. LATE-NC was present in 32% of the participants. It had a significant association with the presence of dementia (OR 2.8, 95% CI 1.7-4.6) and impairment in memory (OR 3.0, 95% CI 1.8-5.1), language (OR 2.6, 95% CI 1.6-4.3), and orientation (OR 3.5, 95% CI 2.1-5.9). The association with impaired orientation was unique to LATE-NC, and the strength and significance of the other associations were comparable to ADNC. Furthermore, we found that history of osteoarthritis (OR 0.37, adjusted 95% CI 0.21-0.66) and hypertension (OR 0.52, adjusted 95% CI 0.28-0.98) were associated with a reduced likelihood of LATE-NC, but not ADNC.DiscussionOur results suggest that LATE-NC is a prevalent degenerative pathology in the oldest-old and has significant associations with dementia and impairment in cognitive domains with magnitudes that are comparable to ADNC. We also found that past medical histories of hypertension and osteoarthritis were associated with a lower likelihood of LATE-NC. This might help identify upstream mechanisms leading to this important pathology. more...

Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0–42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0–4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease. more...

Autoimmune encephalitis (AE) is one of the paraneoplastic syndromes of ovarian teratoma. Insufficient knowledge about the evolution of the disease, as well as its manifestation in the form of non-specific clinical symptoms (such as significant deterioration of memory and cognitive functions of patients), is a common cause of a prolonged diagnostic process and delay in the introduction of targeted treatment. The aim of the study was to summarize the data available in the literature, as well as recent reports, to facilitate and accelerate the diagnosis of the syndrome and ensure better care for patients. more...

Objective: As autoimmune encephalitis (AE) often involves the mesial temporal structures which are known to be involved in both sudden unexpected death in epilepsy (SUDEP) and ictal asystole (IA), it may represent a good model to study the physiopathology of these phenomena. Herein, we systematically reviewed the occurrence of SUDEP and IA in AE. Methods: We searched 4 databases (MEDLINE, Scopus, Embase, and Web of Science) for studies published between database inception and December 20, 2022, according to the PRISMA guidelines. We selected articles reporting cases of definite/probable/possible/near-SUDEP or IA in patients with possible/definite AE, or with histopathological signs of AE. Results: Of 230 records assessed, we included 11 cases: 7 SUDEP/near-SUDEP and 4 IA. All patients with IA were female. The median age at AE onset was 30 years (range: 15–65), and the median delay between AE onset and SUDEP was 11 months; 0.9 months for IA. All the patients presented new-onset seizures, and 10/11 also manifested psychiatric, cognitive, or amnesic disorders. In patients with SUDEP, 2/7 were antibody-positive (1 anti-LGI1, 1 anti-GABABR); all IA cases were antibody-positive (3 anti-NMDAR, 1 anti-GAD65). Six patients received steroid bolus, 3 intravenous immunoglobulin, and 3 plasmapheresis. A pacemaker was implanted in 3 patients with IA. The 6 survivors improved after treatment. Discussion: SUDEP and IA can be linked to AE, suggesting a role of the limbic system in their pathogenesis. IA tends to manifest in female patients with temporal lobe seizures early in AE, highlighting the importance of early diagnosis and treatment. [ABSTRACT FROM AUTHOR] more...

Paraneoplastic neurological syndromes (PNS) are rare and often severe neurological complications of malignancies, significantly impacting patient prognosis and quality of life. They are characterized by a diverse range of onconeural autoantibodies, with further discoveries likely due to ongoing research. Among these, high-risk autoantibodies primarily target intracellular neural cell antigens. We present cases of lung cancer patients who developed limbic encephalitis and seizures at diagnosis, suggestive of PNS. Each case demonstrated distinct autoantibody profiles. Recognition of these potentially life-altering neurological sequelae, as paraneoplastic manifestations of malignancies, is crucial for physicians. PNS may precede primary cancer diagnosis and substantially affect patient presentation and overall outcome. We provide in detail the diagnostic work-up and available treatment options for these complex cases. more...

Background Autoimmune encephalitis (AE) consists of a group of acquired diseases that affect the central nervous system. A myriad of phenotypes may be present at the onset. Due to the heterogeneity of clinical presentations, it is difficult to achieve uniformity for the diagnostic and therapeutic processes and follow-up strategies. more...

The diagnosis of diseases from the group of autoimmune encephalitis (AE) requires a detailed analysis of clinical data and correlation of results from a wide range of laboratory and instrumental research methods. This article presents three clinical cases of patients with AE. In one patient, AE was associated with a malignant neoplasm, in the second one – with the novel coronavirus infection, and in the third patient, no comorbid pathology was detected. The specific type of encephalitis was determined for each of the three patients. The diagnosis of “autoimmune limbic encephalitis” was established in two patients based on visualization of changes in the medial temporal structures in the magnetic resonance imaging of the brain, detection of pathological bioelectrical activity in the temporal lobe cortex in electroencephalography, and pleocytosis in cerebrospinal fluid. The diagnosis of “anti-NMDA receptor encephalitis” was made based on the detection of specific antibodies to the subunit of the corresponding receptor. Neurological deficit regression was observed in two patients after the application of combined immune therapy methods and in one patient without the use of immune therapy. more...

BackgroundParaneoplastic limbic encephalitis is a rare neurologic syndrome that affects patients with cancer and commonly presents with symptoms of personality changes, visual disturbances, seizures, vertigo, and memory loss. It has an immune-mediated pathophysiology and is associated with antibodies directed against both the tumor and limbic structures in the nervous system. Here, we report a case of paraneoplastic limbic encephalitis with an unusual presentation with initial symptoms of panhypopituitarism.Case presentationA 28-year-old Caucasian man with history of testicular cancer in remission for almost 2 years was admitted to our hospital for altered mental status, syncope, vertical gaze palsy, ataxia, and tremor. Three months prior to admission, he began to have initial symptoms of fatigue, weight gain, and hypogonadism. A few weeks before admission, he also developed worsening neurological symptoms that led him to present to the hospital. While hospitalized, he had an episode of syncope. Evaluation of his syncope revealed that he was hypovolemic due to polyuria, concerning for diabetes insipidus. While the patient did not meet criteria for diabetes insipidus, further endocrine laboratory testing to evaluate his central hormonal axes revealed panhypopituitarism. He also underwent a neurologic work-up with brain magnetic resonance imaging and lumbar puncture, with results consistent with encephalitis. He received high-dose steroids, plasmapheresis, and intravenous immunoglobulin, which did not significantly improve his physical examination or mental status. Extensive testing did not show any recurrence of his testicular cancer. Paraneoplastic antibodies were also ordered, with anti-Ma2 antibodies eventually returning positive, consistent with anti-Ma2 paraneoplastic limbic encephalitis.ConclusionParaneoplastic limbic encephalitis is often a difficult diagnosis due to its variable presentation and timeline of presentation, leading to delays in both diagnosis and treatment. While paraneoplastic limbic encephalitis usually presents with neurological symptoms, it may also present with panhypopituitarism. A high index of suspicion is warranted for paraneoplastic syndromes in patients with history of malignancy, even if the malignancy is in remission. more...

Background: Anti-leucine-rich glioma inactivated 1 limbic encephalitis (anti-LGI1 LE) is one of the most frequent autoimmune encephalitis, commonly coexisting with other autoimmune diseases. Rheumatoid arthritis (RA) and monoclonal gammopathy of unknown significance (MGUS) are commonly associated with autoimmune phenomena. However, neither RA nor MGUS have been described in the literature to date as coexisting with anti-LGI1 LE. Case description: We present the case of anti-LGI1 LE in a male patient with rheumatoid arthritis, who was also found to have an MGUS. The patient was initially treated with corticosteroids and IV immunoglobulin. After a mild relapse, his treatment was complemented with rituximab, resulting in complete regression of the disease symptoms. Conclusions: Our report provides evidence for the coexistence of anti-LGI1 LE with RA and/or MGUS, thus extending the differential diagnosis of patients suffering with these disease entities that present with neuropsychiatric symptoms suggestive of encephalitis. Moreover, this case raises challenges on the management of the coexistence of these diseases, given the lack of therapeutic guidelines and their potential interaction on a pathophysiological and a clinical level. more...

In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy, Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with a marked increase in bursting patterns. Finally, mass spectrometry uncovered key modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals. more...

Background: Sleep disorders are a common phenomenon among patients undergoing neurological rehabilitation and should be taken into account in everyday treatment—even in the rare diagnostic group of autoimmune encephalitis (AE). Objectives: The article highlights common sleep disorders in patients with AE. In addition, recommendations for the diagnosis and treatment of sleep disorders in this patient group are given. Materials and methods: The specified literature was used as a basis for preparing the work and presented in a differentiated manner according to the disorder. Results and conclusions: Patients with AE often experience severe sleep disorders, some of which persist even after successful acute treatment of AE. Appropriate diagnosis and treatment of the sleep disorder is important in patients with AE. [ABSTRACT FROM AUTHOR] more...

Background: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. Methods: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. Results: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. Conclusions: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes. [ABSTRACT FROM AUTHOR] more...

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Abstract A 69‐year‐old Japanese male with advanced lung adenocarcinoma developed neurological symptoms after chemoradiotherapy and durvalumab maintenance therapy. He was positive for serum antiamphiphysin antibody, which is rarely seen in patients with lung adenocarcinoma. Additionally, his brain magnetic resonance images showed limbic encephalitis which led to the diagnosis of classic paraneoplastic neurological syndrome (PNS). Immune checkpoint inhibitors (ICIs) activate T cells and may also activate antineuronal antibodies that cause PNS. Durvalumab, which is an ICI, may have led to antiamphiphysin antibody‐positive PNS in our patient. Treatment with systemic high‐dose methylprednisolone was unsuccessful and he died 2 months later. PNS should be considered as one of the differential diagnoses in patients with lung cancer and neurological symptoms during, or after, ICI treatment. more...

In this report, we present a rare case of anti-Ma2-associated encephalitis concurrent with coronavirus disease 2019 (COVID-19) following breast cancer surgery. The patient exhibited minimal clinical symptoms of COVID-19 infection but developed seizures and altered mental status after surgery, leading to diagnosis of a classic paraneoplastic syndrome. This case highlights the possibility of paraneoplastic neurological syndrome even after cancer surgery and the need for careful consideration of post-acute infection syndromes when neurological symptoms occur following an infection. more...

Introduction: Anti-leucine-rich glioma inactivated-1 (LGI-1) is one of few antibodies implicated in limbic encephalitis, a syndrome that can result in permanent neurological symptoms if left untreated.Case Report: We present a patient with dystonic seizures, progressive cognitive decline, psychiatric symptoms and short-term memory loss, and mild hyponatremia diagnosed with anti-LGI-1 antibody limbic encephalitis.Conclusion: There are few reports in the emergency medicine community describing anti-LGI-1 antibody limbic encephalitis. Delay in diagnosis can risk irreversible limbic damage. Therefore, it is important for the emergency physician to be aware of anti-LGI-1 antibody limbic encephalitis when presented with adult-onset seizures and altered mental status of unknown etiology. more...

Background: Anti-LGI1 encephalitis is characterized by a pattern of inflammation that predominantly affects the limbic system It is part of the autoimmune encephalitis that attack neuronal surface antigens. It is characterized by the triad of subacute dementia, faciobrachial dystonic crises, and hyponatremia, presenting an excellent response to immunotherapy. The aim of this article is to describe the clinical evolution and functional outcome at 6 months of two patients with anti-LGI1 encephalitis using clinical cases. Clinical classes: Case 1: 62-year-old man with 8-week symptoms manifested by changes in mood, disorientation, and focal motor seizures. Case 2 A 72-year-old woman with a 5-month evolution of rapidly progressive dementia, hyponatremia and bitemporal hyperintensities on MRI. In both, due to clinical suspicion, acute dual immunotherapy with steroid and immunoglobulin was given with substantial improvement. Subsequently, the existence of anti-LGI1 antibodies in cerebrospinal fluid was confirmed. Although both patients received a dose of rituximab during their hospitalization, only the patient in the first case continued biannual doses of rituximab. The second patient was not initially considered to continue long-term immunomodulatory treatment and experienced a relapse. Conclusions: These clinical vignettes present the reader with the classic characteristics of this disease. This can facilitate its recognition and timely initiation of treatment, improving the functional prognosis of patients. [ABSTRACT FROM AUTHOR] more...

Background and purpose: N‐methyl‐d‐aspartate receptor (NMDAR) and leucine‐rich glioma‐inactivated protein 1 (LGI1) encephalitis are important types of autoimmune encephalitis (AE) with significant morbidity. In this study, we used a proteomic approach in search of novel clinically relevant biomarkers in these types of encephalitides. Methods: Swedish and Czech tertiary neuroimmunology centers collaborated in this retrospective exploratory study. Fifty‐eight cerebrospinal fluid (CSF) samples of 28 patients with AE (14 definite NMDAR, 14 with definite LGI1 encephalitis) and 30 controls were included. CSF samples were analyzed using proximity extension assay technology (Olink Target 96 Inflammation panel). For each CSF sample, 92 proteins were measured. Clinical variables were retrospectively collected, and correlations with protein levels were statistically analyzed. Results: Patients and controls differed significantly in the following 18 biomarkers: TNFRSF9, TNFRSF12, TNFRSF14, TNFβ, TNFα, IL7, IL10, IL12B, IFNγ, CD5, CD6, CASP8, MMP1, CXCL8, CXCL10, CXCL11, IL20RA, and sirtuin 2 (SIRT2). In LGI1 encephalitis, no clinically useful association was found between biomarkers and clinical variables. In the NMDAR encephalitis group, SIRT2, TNFβ, and CD5 were significantly associated with ovarian teratoma. For SIRT2, this was true even for the first patients' CSF sample (SIRT2 without vs. with tumor, mean ± SD = 2.2 ± 0.29 vs. 2.88 ± 0.48; p = 0.007, 95% confidence interval = −1.15 to −0.22; r statistic in point‐biserial correlation (rpb) = 0.66, p = 0.011). SIRT2 was positively correlated with age (rpb = 0.39, p = 0.018) and total hospital days (r = 0.55, p = <0.001). Conclusions: SIRT2 should be investigated as a biomarker of paraneoplastic etiology in NMDAR encephalitis. [ABSTRACT FROM AUTHOR] more...

Autoimmune encephalitis is a relatively new entity consisting of an antibody mediated inflammatory process in the central nervous system predominantly involving the limbic system caused by antibody interaction against specific neuronal antigens. The clinical presentation is variable and the magnetic resonance together with the detection of antineuronal antibodies allow a timely diagnosis. We present a clinical case of autoimmune encephalitis with positive anti-GAD antibodies and consider the imaging and clinical aspects relevant to its diagnosis. [ABSTRACT FROM AUTHOR] more...

The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches. more...

Autoimmune encephalitis (AE) is a rare disease manifested by rapidly progressive shortterm memory loss and other cognitive impairment accompanied by multiple disorders related to the limbic system involvement. The initial symptoms of autoimmune encephalitis may imitate other psychiatric disorders and delay the implementation of an appropriate treatment. The case description of a 15-year-old patient with an initial diagnosis of psychotic disorder has been presented. Because of atypical course of an illness and an ineffective treatment with psychotropic drugs, additional tests were made including serological tests, a cerebrospinal fluid (CSF) analysis and magnetic resonance imaging. Due to the entire clinical picture an autoimmune encephalitis was suspected. The implemented treatment included steroid therapy, intravenous immunoglobulins (IVIG) and plasmapheresis. The treatment regimen was repeated until remission was achieved. [ABSTRACT FROM AUTHOR] more...

A 69‐year‐old Japanese male with advanced lung adenocarcinoma developed neurological symptoms after chemoradiotherapy and durvalumab maintenance therapy. He was positive for serum antiamphiphysin antibody, which is rarely seen in patients with lung adenocarcinoma. Additionally, his brain magnetic resonance images showed limbic encephalitis which led to the diagnosis of classic paraneoplastic neurological syndrome (PNS). Immune checkpoint inhibitors (ICIs) activate T cells and may also activate antineuronal antibodies that cause PNS. Durvalumab, which is an ICI, may have led to antiamphiphysin antibody‐positive PNS in our patient. Treatment with systemic high‐dose methylprednisolone was unsuccessful and he died 2 months later. PNS should be considered as one of the differential diagnoses in patients with lung cancer and neurological symptoms during, or after, ICI treatment. [ABSTRACT FROM AUTHOR] more...

Introduction: Limbic encephalitis is a rapidly progressing disease that presents with seizures, psychiatric symptoms, and recent memory loss. Detection of more than one autoantibody is a rare condition in this disease where an underlying autoantibody is frequently detected. Although different autoantibodies have been reported in the literature, no case has been reported regarding the association of anti-γ- aminobutyric acid-beta-receptor (anti-GABABR) and anti-α-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid (anti-AMPAR). Case: In this presentation, a 46-year-old female patient with subacute development of short-term memory loss and behavioral symptoms will be described. Anti-GABABR and anti-AMPAR were positive in the antineuronal antibody panel sent from the cerebrospinal fluid and serum. Small cell lung cancer was detected as a result of malignancy screening tests. The patient's complaints and autoantibody positivity regressed after immunotherapy. Conclusion: In this case report, a case with coexistence of anti-GABABR and anti-AMPAR antibodies, which has not been previously reported in the literature, is described. As more cases with the coexistence of these two antibodies are detected, knowledge on clinical aspect, laboratory and treatment will increase. [ABSTRACT FROM AUTHOR] more...