Limbic Encephalitis Research Articles

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

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

Candida dubliniensis Meningitis in Immunocompetent Adults - case report and review of literature (P10-10.001)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> We report a case and review the cases of <i>Candida dubliniensis</i> meningitis in immunocompetent adults. <h3>Results:</h3> 32 years old man with history of intravenous drug use (IVDU) presented with seizures, nuchal rigidity, and papilledema. Head CT showed communicating hydrocephalus and brain and spine MR showed diffuse leptomeningeal enhancement extending to the cauda equina. HIV, syphilis, and quantiferon-gold tests were negative but his CD4 count was 203 (430 – 1185/mm3). Lumbar puncture showed opening pressure of 45 mm H2O, CSF protein &gt; 392 mg/dl (15–45), glucose 5 mg/dL (40–70), nucleated cells 246 (0–5), 83% lymphocytes, red blood cells 1 (0–1). CSF meningitis panel was negative, but encephalitis panel showed NMDA receptor antibody. 1,3-Beta-D-glucan was 79 (&lt;60 pg/mL) in the serum and 295 in the CSF and CSF cultures grew <i>Candida dublinens</i>is. <h3>Conclusions:</h3> Chronic base of the skull meningitis has many causes including inflammatory conditions, malignancies, and infections. Invasive <i>C. dublinensis</i> infection is very rare and usually associated with immunodeficiency (HIV or post-transplant). This is the fourth case of <i>C. dublinensis</i> in an immunocompetent host described in the literature. Like our case, in two of those three reports the infection was associated with IVDU, and this information is not available for the third case. This corroborates the hypothesis that IVDU could be a risk factor for this infection. Regarding his CSF NMDA receptor antibody, he did not have limbic encephalitis, dysautonomia, seizures or psychiatric symptoms. There is a known association of this antibody and ovarian teratomas and herpes simplex encephalitis but no association with <i>Candida sp.</i> is known. Despite his low CD4 count he did not have other opportunistic infections. No etiology was identified for this finding. <b>Disclosure:</b> Dr. Horta has nothing to disclose. Dr. White has nothing to disclose. Dr. Greige has nothing to disclose. Dr. Askari has nothing to disclose. Dr. Cervantes-Arslanian has nothing to disclose.

Caspr2 Antibody-Mediated Ataxia, Parkinsonism, and Epilepsy: A Case for Escalating Immunotherapy. (P13-11.007)

<h3>Objective:</h3> To report a rare presentation of anti-Caspr2 syndrome treated successfully with rituximab. <h3>Background:</h3> Anti-Caspr2 syndrome has a variety of clinical phenotypes including encephalopathy, seizure, psychiatric disturbances, respiratory failure, dysautonomia, peripheral nerve dysfunction, as well as ataxia of a constant or episodic nature.¹ In many of the cases with ataxia, there is associated limbic encephalitis.² Anti-Caspr2 syndrome with ataxia, parkinsonism and seizure has only been reported once in the literature.³ This symptomatology can be easily mistaken for an atypical parkinsonism like cerebellar multiple systems atrophy, or spinocerebellar ataxia type 2 but this treatable cause is an important consideration. <h3>Design/Methods:</h3> To report a case of anti-Caspr2 syndrome presenting with pure ataxia, then progressing to parkinsonism, and epilepsy; its successful treatment; and accompanying video examinations. <h3>Results:</h3> A 71 year-old man was referred for 8 months of progressive, generalized ataxia and dysarthria. Immune-mediated ataxia was considered given the subacute course with rapid progression. He was found to have a Caspr2 antibody titer of 1:100. Evaluation for malignancy was unremarkable. Lumbar puncture revealed Caspr2 antibody positivity. The patient was treated with 4 days of intravenous steroids and immunoglobulins with significant improvement. He relapsed four months later with lower extremity weakness and ataxia. Despite maintenance intravenous immunoglobulin, his ataxia continued to progress. He then developed focal seizures with impaired awareness and left sided parkinsonism. He was started on rituximab immunotherapy for ongoing disease activity. His ataxia and parkinsonism significantly improved to near-baseline with continued stability 6 months later. <h3>Conclusions:</h3> This case illustrates an example of an autoimmune-mediated cerebellar ataxia of subacute onset with progression to parkinsonism and epilepsy. Special consideration for anti-Caspr2 syndrome should be taken in cases of progressive ataxia with accompanying neurologic features of parkinsonism and seizure. Escalation to rituximab can be considered for patients who continue to progress despite preliminary immunotherapy. <b>Disclosure:</b> Dr. Sugar has nothing to disclose. Dr. Witek has nothing to disclose.

Acute Fulminant Encephalitis in the Setting of Acute COVID-19 Infection (P12-3.008)

<h3>Objective:</h3> NA <h3>Background:</h3> Encephalitis in the setting of COVID-19 has been reported, however the mechanism by which SARS-CoV-2 causes encephalitis remains unclear. We aimed to describe a case of fulminant limbic encephalitis associated with acute COVID-19 infection. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 33-year-old COVID-19 positive female presented after being found unresponsive with seizure-like activity. On arrival, patient was comatose with intermittent left gaze deviation, weak gag and cough reflexes, and no movement to pain. She was intubated for airway protection (without hypoxia). Continuous EEG demonstrated generalized and bilaterally independent epileptiform discharges, with no electrographic or clinical seizures. Patient was prophylactically started on levetiracetam. Brain MRI revealed scattered DWI and T2 hyperintensities involving supratentorial and infratentorial areas more prominent in temporal lobes. CSF analysis showed mild neutrophilic pleocytosis; protein and glucose were normal. Infectious, autoimmune, and paraneoplastic encephalopathy in CSF/serum panels were negative. CSF COVID-19 PCR was negative. ESR, CRP and ferritin were mildly elevated. High-dose steroids and intravenous immunoglobulin were initiated. After 7 days repeated brain MRI demonstrated progression of T2 hyperintensities including midbrain, cerebral peduncles, and right hemispheric cortical ribboning. Patient continued to decline with gradual loss of brainstem reflexes and downward gaze deviation with ocular bobbing movements. Due to clinical deterioration the patient was transitioned to comfort care and deceased after extubating. <h3>Conclusions:</h3> There have been increasing reports of severe encephalitis subtypes among younger COVID-19 patients commonly associated with poor outcomes compared to other subtypes of encephalitis. To our knowledge this is the first case of encephalitis associated with COVID-19 infection with no response to immunomodulatory therapies. Other possible etiologies in this case include hypoxic injury, hypoglycemia, or toxic insults, which were considered less likely given clinical scenario. In our case, PCR of CSF was negative for COVID-19 which raises possibility of secondary hyperinflammation or molecular mimicry as potential causes. <b>Disclosure:</b> Dr. Kherallah has nothing to disclose. Dr. Manrique has nothing to disclose. Dr. Vennavaram has nothing to disclose. Dr. Samaha has nothing to disclose.

Neuropsychiatric symptoms of autoimmune limbic encephalitis, between neurology and psychiatry

Neuropsychiatric symptoms of autoimmune limbic encephalitis, between neurology and psychiatry

Seizure semiology and predictors of outcomes in Chinese patients with glutamic acid decarboxylase antibody-associated neurological syndrome

BackgroundIn the current study, seizure semiology and potential predictive factors of seizure outcomes in glutamic acid decarboxylase antibody (GAD Ab)-associated neurological syndrome were investigated.MethodsIn this study, 32 Chinese patients with GAD Ab-associated neurological syndrome who presented with seizures at Peking Union Medical College Hospital from January 2017 to October 2022 were reviewed; 30 had a follow-up duration of more than 1 year.ResultsAmong the 32 patients, 10 presented with epilepsy alone. Concomitant neurological syndromes were observed in 22 patients, including limbic encephalitis (n = 20), stiff-person syndrome (SPS, n = 1), and cerebellar ataxia (n = 1). Bilateral tonic–clonic seizures were observed in 21 patients (65.6%). Focal seizures occurred in 27 patients (84.4%); 17 had focal motor seizures and 18 focal non-motor seizures. Among 30 patients with long-term follow-up, 11 (36.7%) were seizure-free. Acute/subacute onset (p = 0.049) and comorbidity of limbic encephalitis with epilepsy (p = 0.023) led to better seizure outcomes. Patients with persistent epilepsy were more likely to have focal seizure (p = 0.003) and higher frequency of seizure (p = 0.001). Furthermore, these patients tended to have longer intervals from onset to immunomodulatory treatments. Early immunotherapy (within 6 months from onset) was administered in 81.8% of seizure-free patients but only in 42.1% of patients with persistent seizures. However, steroid and immunosuppressant duration did not differ in the two groups. Repeated serum GAD Ab tests during the follow-up showed no association with seizure outcomes.ConclusionsThe seizure manifestations are diverse and variable. Approximately one third of patients achieved seizure remission during long-term follow-up. The type and frequency of seizures may influence the seizure outcomes. Early immunotherapy, especially within 6 months, may lead to better seizure outcomes.

Comparative Effects of Domain-Specific Human Monoclonal Antibodies Against LGI1 on Neuronal Excitability.

Autoantibodies to leucine-rich glioma inactivated protein 1 (LGI1) cause an autoimmune limbic encephalitis with frequent focal seizures and anterograde memory dysfunction. LGI1 is a neuronal secreted linker protein with 2 functional domains: the leucine-rich repeat (LRR) and epitempin (EPTP) regions. LGI1 autoantibodies are known to interfere with presynaptic function and neuronal excitability; however, their epitope-specific mechanisms are incompletely understood. We used patient-derived monoclonal autoantibodies (mAbs), which target either LRR or EPTP domains of LGI1 to investigate long-term antibody-induced alteration of neuronal function. LRR- and EPTP-specific effects were evaluated by patch-clamp recordings in cultured hippocampal neurons and compared with biophysical neuron modeling. Kv1.1 channel clustering at the axon initial segment (AIS) was quantified by immunocytochemistry and structured illumination microscopy techniques. Both EPTP and LRR domain-specific mAbs decreased the latency of first somatic action potential firing. However, only the LRR-specific mAbs increased the number of action potential firing together with enhanced initial instantaneous frequency and promoted spike-frequency adaptation, which were less pronounced after the EPTP mAb. This also led to an effective reduction in the slope of ramp-like depolarization in the subthreshold response, suggesting Kv1 channel dysfunction. A biophysical model of a hippocampal neuron corroborated experimental results and suggests that an isolated reduction of the conductance of Kv1-mediated K+ currents largely accounts for the antibody-induced alterations in the initial firing phase and spike-frequency adaptation. Furthermore, Kv1.1 channel density was spatially redistributed from the distal toward the proximal site of AIS under LRR mAb treatment and, to a lesser extant, under EPTP mAb. These findings indicate an epitope-specific pathophysiology of LGI1 autoantibodies. The pronounced neuronal hyperexcitability and SFA together with dropped slope of ramp-like depolarization after LRR-targeted interference suggest disruption of LGI1-dependent clustering of K+ channel complexes. Moreover, considering the effective triggering of action potentials at the distal AIS, the altered spatial distribution of Kv1.1 channel density may contribute to these effects through impairing neuronal control of action potential initiation and synaptic integration.

Anti-amphiphysin encephalitis: Expanding the clinical spectrum.

An analysis of the clinical features of autoimmune encephalitis accompanied by anti-amphiphysin antibodies. The data of encephalitis patients with anti-amphiphysin antibodies were retrospectively evaluated, including demographics, neurological and laboratory findings, imaging, treatment, and prognostic predictions. Ten patients aged between 29 and 78 years (median age 52 years) were included. The male: female ratio was 4:6. Limbic encephalitis was found in nine patients while epileptic seizures were present in seven patients. All patients showed anti-amphiphysin antibody positivity in sera while one ninth was positive for CSF antibody. The EEG findings were abnormal, including reductions in background activity, and the presence of diffuse slow waves, sharp waves, and spikes and waves. Five patients showed signs of increased T2 signals in the medial temporal lobe on MRI while PET showed either hyper- or hypo-metabolic changes in several brain regions, including the temporal lobe, hippocampus, basal ganglia, frontal and parietal cortices. Nine of ten patients were treated with immunotherapy, with improvements of varying degrees. There was a significant reduction in seizure frequency, and all patients were seizure-free at last follow-up. Autoimmune encephalitis with anti-amphiphysin antibodies has a variety of clinical manifestations. The most common symptom is limbic encephalitis. Although relief from seizures can be achieved relatively easily, many patients suffer psychiatric, cognitive, and sleep sequelae. The disease was found to be associated with a lower incidence of cancer than has been previously reported for paraneoplastic neurologic syndromes.

Anti-LGI1 encephalitis: A family affair

Here we describe the second ever-reported case of familial anti-leucine-rich glioma-inactivated protein 1 (LGI1) limbic encephalitis (LE). Two elderly Caucasian sisters presented with psychiatric symptoms and cognitive impairment, followed by faciobrachial dystonic seizures. Anti-LGI1 antibodies were detected in their serum. Considering they had been living in distant regions for decades, environmental factors could be ruled out. Human leukocyte antigen (HLA) genotyping revealed that both carried HLA-DRB1*07, found in 90% of anti-LGI1 encephalitis patients, HLA-DQA1*02:01 and HLA-DQB1*03:03, commonly associated with DRB1*07:01. Considering the exceptional nature of familial cases, as-yet-unknown genetic contributors other than HLA might play a role in our siblings.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes.

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.

Ophelia syndrome as single association: neoplastic limbic encephalitis and Hodgkin lymphoma

Ophelia syndrome as single association: neoplastic limbic encephalitis and Hodgkin lymphoma

Clinical features of 28 cases of anti-leucine-rich glioma-inactivated protein 1 encephalitis and anti-contactin-associated protein-like 2 encephalitis.

Autoimmune encephalitis arising from autoantibodies against leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) are rare and with high clinical heterogeneity. They are easily misdiagnosed and missing diagnosed. This study aims to explore the clinical characteristics, auxiliary examinations, therapies and prognosis of anti-LGI1 and anti-CASPR2 encephalitis. Seventeen anti-LGI1 and 11 anti-CASPR2 encephalitis patients who were admitted to the Department of Neurology, Xiangya Hospital, Central South University between January 2018 and January 2021 were collected and retrospectively analyzed. Autoimmune encephalitis related antibodies and paraneoplastic antibodies were screened in all patients. The clinical manifestations, results of laboratory tests, imaging features, treatments and outcomes of 2 encephalitis groups were analyzed and compared. In the anti-LGI1 encephalitis group, the age of 17 patients was 28-83 (53.18±19.08) years old, and the ratio of male to female was 9꞉8. There were 10 patients with cognitive impairment, 7 seizures, 4 faciobrachial dystonic seizures, and 1 psychiatric disturbance. Hyponatremia was observed in 7 patients. Eight patients had increased slow waves and 5 had epileptic discharge in electroencephalogram (EEG). Brain magnetic resonance (MRI) showed T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR) hyperintense signal in the temporal lobe, hippocampus and basal ganglia in 13 patients. In the anti-CASPR2 group, the age of 11 patients was 17-68 (47.18±16.20) years old, and the ratio of male to female was 5꞉6, with 7 limbic encephalitis, 1 Morvan syndrome, and 3 acquired neuromyotonia (NMT). Three patients had increased slow waves and 2 had epileptic discharge in EEG. Brain MRI showed T2WI and FLAIR hyperintense signal in the temporal lobe, hippocampus in 2 patients. Steroids, intravenous immunoglobin, and plasma exchange were administrated in 16 anti-LGI1 encephalitis and 8 anti-CASPR2 encephalitis patients with good therapeutic responses. Among them, 1 patient with anti-LGI1 encephalitis and 3 with anti-CASPR2 encephalitis were administrated with mycophenolate mofetil for immune maintenance therapy. No recurrences were observed in all patients with immunotherapy except for 2 patients who lost of follow-up. There were significant differences in cognitive impairment, hyponatremia, and brain MRI abnormalities between anti-LGI1 and anti-CASPR2 encephalitis patients (all P<0.05). Limbic encephalitis is a common syndrome in both anti-LGI1 and anti-CASPR2 encephalitis patients. Anti-CASPR2 encephalitis has a wider clinical spectrum than anti-LGI1 encephalitis, presenting as NMT and Morvan syndrome, which has a closer relationship with tumors. Both of these 2 antibodies associated disorders are sensitive to immunotherapy and have a good prognosis.

Metabolic phenotyping of pilomotor seizures in autoimmune encephalitis.

Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP are still unclear. To have a better understanding of IP underlying mechanisms, the current study investigated whole-brain metabolic networks for the analysis of AE-associated IP. Patients with AE and IP diagnosed at our Institute between 2018 and 2022 were selected. We then investigated the brain regions associated with AE-associated IP using positron emission tomography (PET). Anatomometabolic changes (interictal 18 F fluorodeoxyglucose PET) in AE patients with IP were compared with those of AE patients of similar age without IP (p-voxel <0.001, uncorrected). Sixteen patients showed significant IP. The overall IP prevalence was 4.09% of patients with AE and 12.9% of patients with limbic encephalitis. The most common autoantibodies were against LGI1 (68.8%) followed by GAD65 (6.3%), NMDA (6.3%), GABAb (6.3%), CASPR2 (6.3%), and antibodies recognizing both GAD65 and mGLUR5 (6.3%). Most patients responded well to immunotherapy. Analysis of the imaging results at the voxel level showed that patients with IP had hypermetabolic changes in the right inferior temporal gyrus, suggesting involvement of this brain region in IP. Our findings indicate that IP as an uncommon AE-associated manifestations should be recognized. We observed that the metabolic pattern of IP was conspicuous in the right inferior temporal gyrus.

Paraneoplastic Kelch-like protein 11 antibody-associated cerebellar and limbic encephalitis caused by metastatic “burned-out” seminoma – A scar(r)y phenomenon

IntroductionThe diagnosis of paraneoplastic neurologic syndromes is challenging when the primary tumor masquerades as scar tissue (i.e. “burned-out”). MethodsCase report. ResultsA 45-year-old male patient presented with progressive cerebellar symptoms and hearing loss. Initial screening for malignancy and extensive testing of paraneoplastic and autoimmune neuronal antibodies gave negative results. Repeated whole-body FDG-PET CT revealed a single paraaortic lymphadenopathy, metastasis of a regressed testicular seminoma. Anti-Kelch-like protein-11 (KLHL11) encephalitis was finally diagnosed. ConclusionOur case highlights the importance of continued efforts to find an often burned-out testicular cancer in patients with a highly unique clinical presentation of KLHL11 encephalitis.

A feline model of spontaneously occurring autoimmune limbic encephalitis

Autoimmune encephalitis (AE) is an important cause of encephalitis in humans and occurs at a similar rate to infectious encephalitis. It is frequently associated with antibodies against the extracellular domain of neuronal proteins. Among human AE, that with antibodies against leucine-rich glioma-inactivated 1 (LGI1) is one of the most prevalent forms, and was recently described in cats with limbic encephalitis (LE). In this study, we describe a large cohort (n = 32) of cats with AE, tested positive for voltage gated potassium channel (VGKC)-antibodies, of which 26 (81%) harboured LGI1-antibodies. We delineate their clinical and paraclinical features as well as long-term outcomes up to 5 years.Similar to human cases, most cats with LGI1-antibodies had a history of focal seizures (83%), clustering in the majority (88%), with interictal behavioural changes (73%). Among feline AE patients, there was no seizure type or other clinical characteristic that could distinguish LGI1-antibody positive from negative cats, unlike the pathognomic faciobrachial dystonic seizures seen in humans. Although six cats were euthanased in the first year for epilepsy-associated reasons, those attaining at least 1-year survival had good seizure control and quality of life with appropriate veterinary care and medication. Acute-phase immunotherapy (prednisolone) was given to the most severely unwell cases and its effect is retrospectively evaluated in 10 cats. Our data show LGI1-antibodies are an important cause of feline encephalitis, sharing many features with human AE. Further research should examine optimal therapeutic management strategies and the cause of LE in seronegative cats, building on paradigms established in the counterpart human disease.

Elevated IL-6 plasma levels are associated with GAD antibodies-associated autoimmune epilepsy.

Antibodies against glutamic acid decarboxylase (GADA) are present in multiple neurological manifestations, such as stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. Increasing data support the clinical significance of GADA as an autoimmune etiology of epilepsy, however, there is not yet definitive evidence to confirm the pathogenic link between GADA and epilepsy. Interleukin-6 (IL-6), a pro-convulsive and neurotoxic cytokine, and interleukin-10 (IL-10), an anti-inflammatory and neuroprotective cytokine, are crucial inflammatory mediators in the brain. Increased production of IL-6 and its association with epileptic disease profiles are well established, suggesting the presence of chronic systemic inflammation in epilepsy. Therefore, in this study, we investigated the association of plasma cytokine concentrations of IL-6 and IL-10 and their ratio with GADA in patients with drug-resistant epilepsy. Interleukin-6 and IL-10 concentrations were measured by ELISA in plasma, and the IL-6/IL-10 ratio was calculated in a cross-sectional cohort of 247 patients with epilepsy who had their GADA titers measured previously for their clinical significance in epilepsy. Based on GADA titers, patients were grouped as GADA negative (n = 238), GADA low positive (antibody titers < 1,000 RU/mL, n = 5), and GADA high positive (antibody titers ≥ 1,000 RU/mL, n = 4). Median IL-6 concentrations were significantly higher in patients with high GADA positivity [2.86 pg/mL, interquartile range (IQR) = 1.90-5.34 pg/mL] than in GADA-negative patients [1.18 pg/mL, interquartile range (IQR) = 0.54-2.32 pg/mL; p = 0.039]. Similarly, IL-10 concentrations were also higher in GADA high-positive patients [1.45 pg/mL, interquartile range (IQR) = 0.53-14.32 pg/mL] than in GADA-negative patients [0.50 pg/mL, interquartile range (IQR) = 0.24-1.00 pg/mL], however, the difference was not statistically significant (p = 0.110). Neither IL-6 nor IL-10 concentrations were different between GADA-negative and GADA low-positive patients (p > 0.05) or between GADA low-positive or GADA high-positive patients (p > 0.05). The IL-6/IL-10 ratio was also similar among all the study groups. Increased circulatory concentrations of IL-6 are associated with high GADA titers in patients with epilepsy. These data provide additional pathophysiological significance of IL-6 and help to further describe the immune mechanisms involved in the pathogenesis of GADA-associated autoimmune epilepsy.

Neurosyphilis Presenting as Syndrome of Limbic Encephalitis Mimicking Herpes Simplex Virus Neuro-Infection Diagnosed Using CXCL13 Point-of-Care Assay—Case Report

The syndrome of limbic encephalitis is a severe clinical condition with heterogenous aetiopathogenesis. A common pathogen causing the infectious syndrome of limbic encephalitis is herpes simplex virus (HSV), but rare cases caused by Treponema pallidum have also been reported. We present the case of a 46-year-old man who presented with sudden onset of headaches, nausea, vomiting, and short-term loss of consciousness with clonic convulsions and subsequent disorientation and aphasia. Examination of the cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis and magnetic resonance of the brain revealed bilateral temporal lesions. Clinical, radiologic, and biochemical examinations of CSF suggested encephalitis caused by HSV. However, the positivity of CXCL-13 chemokine in the CSF by a rapid point-of-care assay suggested active spirochetal infection and led to further serologic investigation. The definitive diagnosis of neuro-syphilis was concluded by positive intrathecal synthesis of immunoglobulins against Treponema pallidum. Penicillin therapy led to a rapid improvement, and the patient was discharged home after three weeks. Due to memory problems and irritability, after eighteen months, he came for a follow-up neurological and psychological examination. The psychological examination revealed a significant deficit in executive functions and behavioural changes. Neurosyphilis should be considered in the differential diagnosis of limbic encephalitis with lymphocytic pleocytosis in cerebrospinal fluid, and CXCL-13 may help to achieve diagnosis.

Cotard syndrome in anti‐adenylate kinase 5 autoantibodies limbic encephalitis

Clinical and Experimental NeuroimmunologyEarly View CLINICAL LETTER Cotard syndrome in anti-adenylate kinase 5 autoantibodies limbic encephalitis Aldo F. Costa, Corresponding Author Aldo F. Costa [email protected] orcid.org/0000-0002-2075-5289 Department of Neurology, University Hospital Reina Sofía, Córdoba, Spain Correspondence Aldo F. Costa, Department of Neurology, University Hospital Reina Sofía, Menéndez Pidal, s/n Av., Córdoba 14004, Spain. Email: [email protected]Search for more papers by this authorAlba Rodríguez, Alba Rodríguez Department of Neurology, University Hospital Reina Sofía, Córdoba, SpainSearch for more papers by this author Aldo F. Costa, Corresponding Author Aldo F. Costa [email protected] orcid.org/0000-0002-2075-5289 Department of Neurology, University Hospital Reina Sofía, Córdoba, Spain Correspondence Aldo F. Costa, Department of Neurology, University Hospital Reina Sofía, Menéndez Pidal, s/n Av., Córdoba 14004, Spain. Email: [email protected]Search for more papers by this authorAlba Rodríguez, Alba Rodríguez Department of Neurology, University Hospital Reina Sofía, Córdoba, SpainSearch for more papers by this author First published: 17 February 2023 https://doi.org/10.1111/cen3.12746Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Early-onset schizophrenia: an adolescent case report

IntroductionThis is the case of a girl, aged 13, starting on 2021 with a first psychotic episode. Before this episode, her psychiatric history was an adjustment disorder because of scholar bullying, fully recovered before the onset of the current symptoms.ObjectivesTo describe an interesting case of early-onset psychosis.MethodsWe have used the interviews with the patient and her profile in Diraya (the medical database software in Andalucía).ResultsThe first symptoms started 6 months before the first hospitalization, and consisted in mild behavioural disorders, with disobedience and rudenesses, which represented a significant change compared with the previous personality of the patient. 3 weeks before the first admission she abruptly started to experience disconnection, unmotivated laughs, decreaded academic performance and incoherent speech. Also, she showed motor symptoms, consisting in oral and right-hand stereotypies. Then, she was hospitalized in a Pediatric unit, in order to rule out organicity. The nuclear magnetic resonance showed an image suggestive of venous development anomaly, with no acute injuries. Her cerebral spinal fluid was widely studied, and all the results were negative, including: the technique of PCR for many virus and bacteria that can cause meningitis or encephalitis; a bacterial culture; a biochemical study; antineuronal antibodies; and a limbic encephalitis antibodies study. Besides, the blood count, the biochemistry, the gasometry and serology were also negative. No drugs were detected in the urinalysis. Once the organicity was ruled out, she was treated with Olanzapine and Diazepam, and destinated to my child and adolescent psychiatry unit. During the first hospitalization we observed that she looked very often to the mirror, showed soliloquies and took leaps. During the interviews she was desinhibited. She initiated a delusional speech, focused in sexual topics. She said that she’s had a baby in the future with his father, and talked a lot about things she had already made in the future. During this admission, we changed the treatment to Quetiapine and Valproate.The second hospitalization was was done due to a lack of efficacy with the previous treatment and the presence of autolytic thoughts. We switched from Quetiapine to Aripiprazole. After a few days, she showed again a desinhibited behaviour, and kept the delusional speech, that now was more complex, refering that she had more than 20 babies, with many different men. After this we tried Lurasidone and suspended Aripiprazole, she showed a clinical improvement, at the cost of many side effects, though. So we finally changed to Clozapine, in combination with Gabapentin. Since she got clinical levels of clozapine, the delusions have been encapsulated.ConclusionsThe differential diagnosis is set with an early-onset schizophrenia and a schizoaffective disorder. Obviously, the evolution of the sypmptoms in the following months and years will have the last word.Disclosure of InterestNone Declared

Exploring the concept and management of post ictal psychosis through a clinical case and review

IntroductionPostictal Psychosis of Epilepsy (PIPE), part of the group collectively known as Psychosis of Epilepsy, is characterized by an onset of confusion or psychotic symptoms within one week of apparent normal mental function. PIPE has been argued to be underdiagnosed in the clinical population, perhaps due to a failure to recognize the temporal relation between the seizure and the psychotic episode.ObjectivesTo explore the concept and management of post ictal psychosis.MethodsWe present a clinical case and a review of the literature concerning post ictal psychosis.Results We report the case of a 36 year old woman with focal refractory epilepsy after a likely episode of limbic encephalitis in 2015. Cognitive and psychiatric sequelae in the form of depressive symptoms, in treatment with neurology and psychiatry since 2021. One previous episode of psychotic symptoms during seizures. Worsening of seizure frequency since march of 2022 with apparent normalization (absence of seizures after dose reduction of eslicarbamazepine and introduction oflamotrigine) for about four days before being hospitalized in the neurology unit due tobehavioral abnormalities. During psychiatric exploration, the patient showed signs of partial clouding of consciousness with manierisms, ecopraxias and ecolalias; verbigerance in the form of the neurologist’s name and bizarre movements like looking behind suggestive of sensoroperceptive disturbances. The symptomatology resolved itself during the following week after treatment with diazepam.Finally, a narrative review concerning the case was also performed; with particular emphasis on antipsychotic drugs with low risk of lowering seizure threshold (such as risperidone or aripiprazole) as the recommended treatment.ConclusionsOur findings point to the relevance of Postictal Psychosis of Epilepsy as a clinical entity. Further studies on pathogenic mechanisms and therapeutic management are required.Disclosure of InterestNone Declared