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Autoimmune epilepsy in children: Case series and proposed guidelines for identification - Suleiman - 2013 - Epilepsia - Wiley Online Library

Summary Purpose Antibodies against neuronal surface proteins are increasingly recognized in autoimmune central nervous system (CNS) disorders in which seizures are the main or an important feature. The disorders include antibody‐associated limbic encephalitis and N‐methyl‐D‐aspartate receptor (NMDAR)encephalitis; however, seizures of autoimmune etiology may exist beyond the spectrum of these recognized syndromes. Because these seizures are potentially treatable with immune therapy, guidelines are needed to help in their early recognition. Methods We describe 13 representative children seen at our tertiary institution over a period of 3.5 years with suspected autoimmune epilepsy. Autoimmune epilepsy was suspected clinically when there was any of the following: (1) recognizable syndromes such as NMDAR encephalitis or limbic encephalitis, (2) evidence of CNS inflammation in cerebrospinal fluid or on magnetic resonance imaging (MRI), (3) the presence of other autoimmune diseases, or (4) positive response to immunotherapy. We tested these patients for neuronal surface antibodies (voltage gated potassium channel [VGKC]‐complex, leucine rich glioma inactivated 1 [LGI1], contactin‐associated protein‐like 2 [CASPR2], and NMDAR) and glutamic acid decarboxylase (GAD) antibodies. We modified the J Neurol Neurosurg Psychiatry, 83, 2012, 638 guidelines that were designed to classify adults with neuronal surface antibody syndromes (NSAS), to be more appropriate for children with suspected autoimmune epilepsy. Using the modified guidelines, the 13 patients were classified into definite, probable, possible, unlikely, or unknown autoimmune epilepsy according to the presence of neuronal surface or GAD antibodies, and the response to immune therapy when given. Key Findings Of the 13 patients, 11 were females, and the mean age was 6 years (range 1–13 years). Three patients had classical NMDAR encephalitis, two had VGKC encephalitis, two had limbic encephalitis with negative antibodies, three had epilepsy with other autoimmune diseases (one with high titer GAD antibodies), two had fever‐induced refractory epileptic encephalopathy in school‐aged children (FIRES), and one epileptic encephalopathy associated with VGKC antibodies. Seven patients of the 13 children with suspected autoimmune epilepsy were positive for neuronal surface antibodies (NMDAR, n = 3; VGKC‐complex, n = 3; and GAD, n = 1). Immunotherapy was given to nine cases, and a positive response was more common in patients with positive neuronal surface antibodies (5/5) compared to those with negative antibodies (2/4). Applying the proposed guidelines, the classification of autoimmune epilepsy was definite in five, probable in one, possible in three, unlikely in two, and unknown in two patients. Significance Neuronal surface antibodies and GAD antibodies are present in a proportion of children with suspected autoimmune epilepsy and may define a treatable subgroup of childhood epilepsy. The proposed guidelines can be useful in the recognition of children with seizures of autoimmune etiology. The association between autoantibodies and central nervous system (CNS) disease is increasingly recognized. Serum and cerebrospinal fluid (CSF) antibodies that bind to neuronal cell surface proteins including channels and receptors have the potential to be pathogenic and cause CNS disease. By contrast onconeuronal antibodies are typically targeted against intracellular antigens and not thought to be directly pathogenic (Vincent et al., 2011; Bien et al., 2012). Recently antibodies that bind extracellularly and are associated with CNS disorders have been called “neuronal surface antibodies” (NSAbs) and the disorders associated with these NSAbs are called “neuronal surface antibody syndromes” (NSAS) (Zuliani et al., 2012). There are well‐defined CNS syndromes associated with NSAbs where seizures are an important feature. Examples include N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis in which 76–83% of patients will have focal, focal dyscognitive, or generalized seizures (Dalmau et al., 2007, 2008, 2011; Irani & Vincent, 2011), and voltage‐gated potassium channel (VGKC)‐complex antibody associated autoimmune limbic encephalitis (including leucine rich glioma inactivated 1 [LGI1] and contactin‐associated protein‐like 2 [CASPR2] antibodies) in which patients often have temporal lobe seizures (Irani et al., 2010; Lai et al., 2010). In addition, faciobrachial dystonic seizures are seen in adults in association with LGI1 antibodies and often precede the onset of the limbic encephalitis (Irani et al., 2011). Other NSAbs are less frequently found in adults with limbic encephalitis such as alpha amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) and γ‐aminobutyric acid B (GABAB) receptor antibodies (Lai et al., 2009; Lancaster et al., 2010; Boronat et al., 2011). Antibodies to glutamic acid decarboxylase (GAD) have been associated with limbic encephalitis (Malter et al., 2010). Although GAD is an intracellular antigen and therefore GAD Abs themselves may not be pathogenic, it is possible that unrecognized NSAbs coexist with GAD Abs (Zuliani et al., 2012). Zuliani et al. proposed guidelines for the recognition, testing, and treatment of suspected autoimmune CNS disorders. They used clinical criteria, supportive features, neuronal antibody testing, and the response to immune therapy to classify patients into categories of definite, probable, and possible NSAS (Zuliani et al., 2012). Lancaster and Dalmau have proposed an alternative laboratory‐based algorithm for identification and assessment of antibodies to neuronal cell‐surface antigens using cell based assays as well as rat brain immunohistochemistry and cultures of neurons for serum and CSF antibody binding (Lancaster & Dalmau, 2012). In children, NMDAR encephalitis is well described (Florance et al., 2009), whereas limbic encephalitis has been described in association with a number of different autoantibodies including VGKC‐complex Abs (Haberlandt et al., 2011; Suleiman et al., 2011a). In children there are other epileptic conditions where immune‐mediated mechanisms are suspected such as febrile infection‐related epilepsy syndrome (van Baalen et al., 2010) or fever‐induced refractory epileptic encephalopathy in school‐aged children (Nabbout et al., 2010, 2011), both called fever‐induced refractory epileptic encephalopathy in school‐aged children (FIRES). Previous terms used to describe similar syndromes include devastating epileptic encephalopathy in school‐aged children (DESC) (Mikaeloff et al., 2006) and acute encephalitis with refractory repetitive partial seizures (AERRPS) (Sakuma, 2009). These conditions are characterized by new‐onset refractory focal status epilepticus, preceded by fever or infection in previously normal children, followed by a chronic phase of refractory focal epilepsy and severe neurologic impairment (Sakuma et al., 2010). The cause of these conditions is unknown and underlying immune mechanisms have been proposed (Sakuma et al., 2010; Specchio et al., 2010; Nabbout et al., 2011) but not proven. Herein we present a representative case series of 13 children suspected to have an autoimmune basis for their epilepsies. We propose modified guidelines for the recognition of autoimmune epilepsy and apply these guidelines to the 13 children with suspected autoimmune epilepsy to test their utility. Methods Cases identification Through our clinical practice at The Children Hospital at Westmead (CHW) we identified cases with seizures that may have an autoimmune etiology. The neurology department at CHW is a busy tertiary children's hospital that sees 300–400 children with new onset seizures per year, as well as other acute and chronic neurologic diseases in children. The patients presented in this cohort were discussed in detail by JS and RCD as they were suspected to have an autoimmune cause of their epilepsy (as defined below), and were investigated for neuronal surface antibodies. This cohort does not represent all children with encephalitis (of all etiologies) seen during this time (n = 33) and are currently being tested in a separate study at this hospital. It is also likely that other autoimmune epilepsies were missed by the investigating team and were not tested for antibodies. Instead this cohort should be considered a representative sample of children with suspected autoimmune epilepsy, which were used to test the utility of the modified guidelines. We suspected autoimmune epilepsy in children with acute or subacute onset of seizures once other causes (infection, structural, metabolic, or genetic) were excluded, and when any of the features described in Table 1 were present. The following two clinical criteria are used to suspect autoimmune epilepsy associated with NSAbs and GAD antibodies (both are needed) Acute or subacute (<12 weeks) onset of symptoms. Exclusion of other causes (CNS infection, trauma, toxic, tumor, metabolic, previous CNS disease). The following supportive features would strengthen the suspicion of autoimmune epilepsy (patients should have at least 1 of the following): The presence of a well‐defined clinical syndrome such as NMDAR or limbic encephalitis CNS inflammation manifested by at least one of: CSF pleocytosis (defined as >5 white cells/mm3) or presence of oligoclonal bands, elevated IgG index, or elevated neopterin (defined as >30 nm) MRI abnormality compatible with an inflammatory or autoimmune encephalitis including increased signal in the mesiotemporal lobe (LE – like syndrome) Inflammatory neuropathology on biopsy History of other antibody mediated condition (e.g., myasthenia gravis), organ specific autoimmunity or other autoimmune disorders.a Response to immunotherapy a It is recognized that epilepsy is more common in many autoimmune disorders including multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus (T1DM), celiac disease, and autoimmune thyroid disease (Vincent & Crino, 2011). Herein we describe 13 representative patients seen over a three and a half year period (late 2008 to mid‐2012), who we suspected may have an autoimmune cause for their epilepsy, and who had serum available for testing for neuronal antibodies. No patients have been previously reported except for case 5 (Suleiman et al., 2011a) and case 10 (Suleiman et al., 2011b), and these two cases were included as they test the utility of the guidelines. This study was approved by the hospital ethics committee. Ten patients had serum testing in the acute phase of their illness, whereas in three the serum was from the chronic symptomatic phase. All samples were taken before immune therapy, if given. Antibody assays were all performed in Oxford, United Kingdom using previously published methods (Irani et al., 2010), apart from case 3, for which the assay was performed in National NMDAR antibody referral laboratory (Brisbane, Qld, Australia). Proposed modified guidelines To improve recognition and diagnosis of children with suspected autoimmune epilepsy, we modified the guidelines proposed by Zuliani et al. for identification of children with neuronal surface antibodies syndromes (Table 1). Then, based on antibody testing and the response to immunotherapy (when given), we proposed five categories for classification (in descending order of likelihood of autoimmune epilepsy) including definite, probable, possible, unlikely, or unknown autoimmune epilepsy (Table 2, Fig. 1). We applied the modified guidelines to our 13 cases to test their usefulness (Table 3). Classification categories expressing the likelihood of autoimmune epilepsy based on the presence of NSAbs and GAD Abs and the response to immunotherapy (see Fig. 1): Definite autoimmune epilepsy is present if: Known NSAbs are present in serum or CSF AND there is response to immunotherapy Probable autoimmune epilepsy is present if Known NSAbs are present and no immunotherapy responsiveness demonstrated (immunotherapy unsuccessful or not given) OR GAD antibodies are present AND there is response to immunotherapy Possible autoimmune epilepsy is present if known NSAbs are negative and GAD antibodies are present and no immunotherapy responsiveness demonstrated (unsuccessful or not given) OR GAD antibodies are negative and there is a response to immunotherapy Unlikely autoimmune epilepsy is present if Known NSAbs and GAD are negative and there is no response to immunotherapy Unknown autoimmune epilepsya is present if Known NSAbs and GAD are negative and immunotherapy is not given a Patients in this category may move to a different category if they receive immunotherapy, such as “possible” if they respond or “unlikely” if they did not respond to immunotherapy. Case Age (years)/sex Epilepsy diagnosis Acute or sub‐acute onset Seizure type Associated features CSF inflammation (pleocytosis/OCB/neopterin) MRI inflammatory changes Presence of autoimmune/Ab mediated disease NSAbs/GAD Abs Response to immune therapy Outcome Guideline classification 1 3/F NMDAR encephalitis + Focal dyscognitive Encephalopathy, aphasia, dystonia, emotional lability, relapse −/+/+ − − NMDAR CSF and serum + (steroid, IVIG, mycophenolate) Relapse, normal in between Definite 2 6/M NMDAR encephalitis + Focal dyscognitive Encephalopathy, agitation, chorea, dystonia +/−/+ − − NMDAR CSF and serum + (steroid and IVIG) Recovery Definite 3 7/F NMDAR encephalitis + Focal dyscognitive Encephalopathy, agitation, irritability, dyskinesia, fever +/− /ND + − NMDAR CSF and serum + (steroids, IVIG) Recovery Definite 4 1/F VGKC encephalitis + Focal dyscognitive, focal motor with automatism Encephalopathy, fever, respiratory infection +/ND/+ + − VGKC serum (421 pm) Not given Recovery Probable 5 15/F VGKC encephalitis + Focal, secondary generalized tonic–clonic, status epilepticus, Encephalopathy, memory deficit, fever +/−/+ − − VGKC serum (640 pm) + (steroids, IVIG) Relapse, normal in between Definite 6 12/F Limbic encephalitis + Focal dyscognitive Encephalopathy, lethargy, behavioral alteration ND + +/− (ANA) Negative Not given Cognitive, psychiatric impairment Unknown 7 15/F Limbic encephalitis + Focal dyscognitive, secondary generalized tonic–clonic Encephalopathy, cognitive deficits, fever +/−/+ − − Negative + (steroid) Recovery Possible 8 3/M FIRES + Focal, status epilepticus Encephalopathy, irritability, fever, rash, −/−/+ − − Negative − (steroids, IVIG, rituximab) Severe neurologic disability, refractory epilepsy Unlikely 9 8/F FIRES + Focal, secondary generalized Encephalopathy, headache, confusion, fever +/−/+ +/− − Negative − (steroids) Severe neurologic disability, refractory epilepsy Unlikely 10 1/F Epileptic encephalopathy + Epileptic spasms Encephalopathy, developmental delay −/+/+ − − VGKC serum (201 pm) + (steroids) Developmental delay Definite 11 13/F Suspected autoimmune epilepsy + Myoclonic, generalized tonic–clonic (JME) Hyperthyroidism ND − + (Grave's disease and T1DM) Negative Not given Ongoing epilepsy Unknown 12 3/F Suspected autoimmune epilepsy + Focal dyscognitive Myasthenia ND − + (MG) Negative + (steroids) Steroid dependent myasthenia Possible 13 4/F Suspected autoimmune epilepsy + Absence Ataxia −/ND/ND No + (T1DM) GAD (3,000 U/ml) Not given Cognitive impairment, ongoing epilepsy Possible FIRES, fever‐induced refractory epileptic encephalopathy in school‐aged children; JME, juvenile myoclonic epilepsy; OCB, oligoclonal bands; ND, not done; T1DM, type 1 diabetes mellitus; MG, myasthenia gravis; NSAb, neuronal surface antibody. Encephalopathy is defined by the presence of acquired reduction in consciousness, cognitive dysfunction, or behavioral change lasting more than 24 h, and not related to the postictal state, +: present or positive, −: absent or negative. Abnormal ranges: Pleocytosis: CSF white blood cells >5 cells/mm3, Neopterin elevated >30 nm, VGKC serum >100 pm, High titer cutoff for GAD antibodies in neurologic disease is 1,000 U/ml. The main differences to the Zuliani et al. guidelines for adults include the following: In children a paraneoplastic cause of epilepsy is very rare, and testing for onconeural antibodies is rarely necessary. However; children with positive NMDAR Abs should be screened for ovarian teratomas. In children fever and intercurrent infections are common and less likely to be a supportive feature for an autoimmune process as has been proposed in adults, so this was not used as one of the supportive features (Zuliani et al., 2012). We used elevated CSF neopterin as an additional marker of CNS inflammation (Dale et al., 2009). In Zuliani et al., abnormalities on functional imaging including hypermetabolism on positron emission tomography or hyperperfusion on single proton computed tomography were used as features to suggest CNS inflammation. However, there is inadequate research to demonstrate their ability to discriminate epilepsy etiologies in children and therefore we did not include these features. Antibodies included in the guidelines are those available at international laboratories including antibodies against VGKC‐complex proteins, LGI1 and CASPR2, NMDAR, and GAD. We did not include neuronal binding or neuropil antibody testing (using immunohistochemistry or immunofluorescence on rat brain tissue) for recognizable staining patterns (Lancaster & Dalmau, 2012), as these are done in research settings and are less available to clinicians routinely. Response to immunotherapy was defined as significant clinical improvement of encephalopathy or reduction of seizures as judged by the treating clinicians. We accept the subjective nature of this, and the fact that there are a number of confounders that could be responsible for improvements such as the concomitant change in antiepileptic drugs. We incorporated patients who did not receive immunotherapy into the classification either because an immune‐mediated mechanism was not initially suspected or because of spontaneous improvement. Results The 13 patients with seizures of suspected autoimmune origin (11 female, age range 1–13 years, mean age 6 years) are presented in Table 3. All patients had other potential causes for their seizures excluded. All 13 patients had new‐onset seizures and at least one supportive feature of CNS inflammation or the presence of other autoimmune diseases (Tables 1 and 2). Three patients had the clinical characteristics of NMDAR encephalitis (all with CSF and serum NMDAR antibodies), two had encephalitis associated with VGKC‐complex antibodies, two had features suggestive of limbic encephalitis (with negative antibodies), three had epilepsy in association with other autoimmune diseases (one with GAD antibodies), two had FIRES, and one had epileptic encephalopathy with CNS inflammation (VGKC antibody positive). Seven patients (53.9%) of the 13 were positive for one of the tested antibodies including NMDAR (n = 3), VGKC‐complex (n = 3), and GAD (n = 1). Immunotherapy was given in nine patients: five with positive neuronal antibodies and four negative. The immune therapy was steroids alone (n = 4), steroids and intravenous immunoglobulin (IVIG) (n = 3), steroids, IVIG and mycophenolate (n = 1) and steroids, IVIG, and rituximab (n = 1). All five patients with positive neuronal antibodies who received any immune therapy improved after receiving therapy, whereas only two of four with negative neuronal antibodies improved after receiving immune therapy. Three of the four patients who did not receive immunotherapy had poor outcome including ongoing epilepsy, and cognitive and psychiatric impairment (Table 3). Patients were classified according to the proposed modified guidelines (Table 2, Fig. 1), and their classification is presented in Table 3. Five patients had definite, one had probable, three had possible, two had unlikely, and two had unknown autoimmune epilepsy. We present the case histories for 8 of the 13 patients in details in the Data S1 as representative examples. Discussion The recognition of immune mechanisms in neurologic disorders is important as this can prompt early treatment and may lead to better outcomes. The identification of specific and potentially pathogenic NSAbs is increasing, and the spectrum of the clinical syndromes associated with NSAbs is widening (Zuliani et al., 2012). Recently guidelines have been developed to help in the diagnosis and management of adults with suspected NSAS (Zuliani et al., 2012). In children the lack of large studies regarding NSAbs and their related syndromes makes it harder to identify these cases; therefore, guidelines may help in the identification of NSAS particularly when seizures are an important feature. In this paper, we describe 13 representative patients with seizures of suspected autoimmune etiology and we propose features for identification of these pediatric patients, and a classification system testing the strength of evidence of autoimmune epilepsy based on the presence of neuronal antibodies and response to immunotherapy. There were some general features common to the cohort. Females were over‐represented in this cohort, as is often described in autoimmune disorders in general. The seizures were often focal, and generally occurred in association with encephalopathy or other features of CNS dysfunction. Three cases had typical features of NMDAR encephalitis in children, as represented by case 3 description in the Data S1. The patients with NMDAR encephalitis generally had focal epilepsy, and the presence of psychiatric manifestations, behavior alteration, and movement disorder was a strong indicator of NMDAR encephalitis. However, it is possible that NMDAR Abs are present in children with epilepsy in the absence of the classic phenotype as has been described in adults (Niehusmann et al., 2009), and therefore testing for NMDAR Abs in children with suspected autoimmune seizures may provide further information about the spectrum of NMDAR antibody‐associated disease. Two cases had VGKC‐complex Ab‐associated encephalitis, characterized by fever‐associated focal seizures and status epilepticus; one was previously reported (case 5) and the clinical phenotype of the second case (case 4) was similar to our previously reported pediatric patients with VGKC‐complex Ab‐associated encephalitis (Suleiman et al., 2011a). The seizure semiology was suggestive of temporal lobe onset, a finding that is commonly seen in both adults and children with this syndrome (Vincent et al., 2004; Suleiman et al., 2011a). In case 4, mycoplasma immunoglobulin M (IgM) was positive and was consistent with acute infection. Mycoplasma infection has been described in association with NMDAR encephalitis in children and may be a trigger of autoimmune CNS disorders (Florance et al., 2009). However, mycoplasma pneumonia is a common respiratory infection in children and positive mycoplasma serology may therefore be incidental in some patients (Waites & Talkington, 2004). Antibodies against LGI1 or CASPR2, which have been identified as the target of VGKC‐complex Abs in adults, were negative in this case, a finding that is common in children with positive VGKC‐complex Abs. It is possible that in children, VGKC‐complex Abs are targeted against other antigens in the VGKC‐complex that are yet to be identified. Patients with VGKC‐complex Ab‐associated encephalitis often respond to immune therapy, but spontaneous improvement can also occur (Irani et al., 2010) as was the case in this patient. Case 6 had a syndrome of limbic encephalitis; however, NSAbs and GAD Abs were negative, possibly due to late testing and because the patient received no immunotherapy, the classification was “unknown.” Early recognition, testing, and treatment might have improved her outcome. Case 7 had a limbic encephalitis syndrome and was negative for NSAbs but responded to immune therapy (classification possible). Antibodies against AMPAR and GABABR (not tested) or other unrecognized NSAbs could be the cause of limbic encephalitis in these patients. The diagnosis of limbic encephalitis can be challenging in children, where its existence is reported but probably underrecognized (Haberlandt et al., 2011). The diagnosis of limbic encephalitis is partly clinical, with new‐onset temporal lobe seizures and cognitive disturbance sometimes associated with radiologic mesial temporal or hippocampal changes. Because hippocampal signal change is described in a proportion of children with febrile status epilepticus (Shinnar et al., 2012), it is difficult to discriminate radiologic seizure‐induced hippocampal swelling from limbic encephalitis. Cases 8 and 9 were typical of “FIRES” (van Baalen et al., 2010; Nabbout et al., 2011). Neuronal antibodies were negative, and there was no response to immunotherapy in both patients. The absence of antibodies and the negative response to immune therapy make an autoimmune etiology “unlikely.” Negative response to immunotherapy has been reported in a series of seven cases of FIRES, and NSAbs were negative in the tested patients (three were tested for VGKC‐complex Abs and one for NMDAR Abs) (Howell et al., 2012). In addition a series of 12 children with FIRES was negative for neuronal surface antibodies and GAD (van Baalen et al., 2012). There is one report of a boy with positive VGKC antibodies associated with FIRES who benefited from immunotherapy (Illingworth et al., 2011); however, this case did not have a typical course of FIRES and it is possible that the case had VGKC‐complex antibody‐associated encephalitis instead. The markers of CNS inflammation seen in our two cases (8 and 9) have been reported in the acute phase of FIRES, and may be explained by the extreme high seizure load, seizure‐related neuronal injury, or cytokine release (Howell et al., 2012). Rather than an autoimmune epilepsy syndrome, FIRES may be a genetic channelopathy or a chronic epilepsy syndrome with explosive onset (Ismail & Kossoff, 2011; Howell et al., 2012). Three of our cases had epilepsy in association with other autoimmune diseases including type 1 diabetes mellitus (T1DM) and autoimmune thyroid disease (case 11), anti MuSK myasthenia gravis (case 12), and T1DM and possible autoimmune ataxia (case 13). T1DM is a T cell–mediated autoimmune disorder, and there is an increased prevalence of epilepsy in children with this disease (Schober et al., 2012). Seizures can occur in Hashimoto's encephalopathy, which is a rare association of autoimmune Hashimoto's thyroiditis associated with Abs against thyroid peroxidase and thyroglobulin (Castillo et al., 2006). Patients described with Hashimoto encephalopathy present with broad clinical manifestations and are classically reported to be steroid responsive. The role of thyroid antibodies in Hashimoto encephalopathy is uncertain, and the term “steroid responsive encephalopathy associated with autoimmune thyroiditis” (SREAT) has been used to reflect the hypothesis that Hashimoto encephalopathy may be caused by unidentified neuronal autoantibodies (Castillo et al., 2002; Schauble et al., 2003). Graves' disease is an antibody mediated autoimmune disorder and juvenile myoclonic epilepsy (JME) has been previously associated with Grave's disease, and may be due to thyroxine causing a lower seizure threshold (Su et al., 1993). Our case 11 was diagnosed to have an idiopathic myoclonic epilepsy (JME) based on her age, seizure phenotype, and EEG abnormality. JME is considered to be a genetic epilepsy, and indeed in this case there was limited evidence that the epilepsy was autoimmune despite the presence of other autoimmune diseases, and her classification was “unknown” as she was negative for NSAbs and received no immunotherapy. Seizures in association with anti MuSK Ab myasthenia gravis are rare but have been reported in an adult patient (Bhagavati et al., 2007). Case 12 had anti‐MuSK Ab associated myasthenia gravis and concurrent focal epilepsy. Her seizures did not respond to carbamazepine but improved when high dose steroids were used to treat her myasthenia gravis. It is possible that myasthenia gravis and epilepsy in our patient is a chance association, although both clinical entities presented, remitted and relapsed concurrently. Case 13 had seizures in the context of T1DM. This patient had an acute transient ataxia followed by chronic epilepsy, with very high GAD antibodies. GAD antibodies are associated with a variety of CNS syndromes including stiff person syndrome, immune ataxia, epilepsy, and limbic encephalitis (Honnorat et al., 2001; Saiz et al., 2008; Malter et al., 2010). In our patient the immune‐mediated ataxia, cognitive impairment, focal epilepsy, and high GAD antibodies were supportive of the autoimmune epilepsy hypothesis. Patients with epilepsy and other systemic autoimmune diseases may have other as‐yet‐unidentified NSAbs. However, other explanations for increased epilepsy incidence in systemic autoimmune disorders include incidental coexistence, a common genetic predisposition, or secondary effects of the primary disease (Vincent & Crino, 2011). One important feature of the adult guidelines is that response to immunotherapy is used as a retrospective feature to help with classification. In other words the “guideline classification” cannot be completed until immunotherapy is used. Our modified guidelines partly address this issue and incorporate patients who did not receive immunotherapy. In our case, series some patients did not receive immunotherapy either because an autoimmune etiology was not initially suspected at presentation or due to spontaneous improvement without the need for immunotherapy. A positive response to immunotherapy was more common in patients who had positive NSAb (five of five given immunotherapy) compared to those who were NSAb negative (two of four). However, in a recent study of 48 children with suspected autoimmune encephalitis, only 21 had specific antibodies detected, and beneficial treatment responses were seen in both antibody‐positive and antibody‐negative groups (Hacohen et al., 2012). In our clinical practice over the last few years we have been increasingly using immunotherapy empirically once an underlying immune‐mediated disorder is suspected while awaiting the specific investigations. Children suspected of potential autoimmune epilepsy undergo investigations to exclude infectious, toxic, metabolic, or genetic causes, and neuronal surface and GAD antibodies are requested. While awaiting the results of the neuronal antibodies, empiric immunotherapy may be commenced if the clinical syndrome is severe and impairing. We suggest that immunotherapy be used early in the disease course to optimize its potential effect. The regimen we have been using includes intravenous pulse methylprednisolone at 30 mg/kg/day for 3 days followed by a tapering course of oral prednisolone (variable duration of weeks to months according to the disorder), often in conjunction with intravenous immunoglobulins at 2 g/kg given over 2 days. Patients with partial response or no response after 1–3 weeks may receive further doses of intravenous immunoglobulins or plasma exchange if the condition is severe and concerning, and the autoimmune hypothesis remains possible. Patients who fail to respond or who have a partial response may be considered for second‐line therapy, such as rituximab or cyclophosphamide. However the side effect profile of these drugs is more concerning, so a “risk versus benefit” assessment is necessary. In our case series immunotherapy was generally tolerated well, particularly when given short term (such as the NMDAR encephalitis cases). Two patients developed significant side effects attributed to immunotherapy including behavioral alteration with prolonged steroid use (case 12) and prolonged hypogammaglobulinemia requiring IVIG replacement presumed to be secondary to rituximab (case 8), a finding that has been described previously (Makatsori et al., 2012). Some patients with seizures of autoimmune etiology can have complete recovery without immunotherapy (similar to case 4); however, it is hard to predict which cases will spontaneously recover, and therefore early immunotherapy is suggested when the patient is severely impaired. Similar treatment regimens have been used in adults with VGKC Ab‐positive encephalitis with good effect (Reid et al., 2009; Wong et al., 2010). Although plasma exchange is used commonly in adults, the use of plasma exchange in children as a modality of immune therapy is limited due to its invasiveness, the need for intensive care treatment, and potential side effects. Although a positive response to immunotherapy supports immune‐mediated mechanisms, steroids (and IVIG to a lesser extent) are used in the treatment of refractory and severe epilepsies that are not proven to be autoimmune. In conclusion, autoimmune mechanisms play an important role in a proportion of children presenting with seizures. We propose guidelines that may help clinicians in the approach to identify children with suspected autoimmune seizures. Although helpful, the guidelines are not perfect and represent only an attempt to identify and classify these patients. These guidelines do not predict treatment responsiveness or outcome. Future studies may improve the understanding of clinical phenotypes of autoimmune epilepsy in children and help further develop syndrome‐specific and treatment‐oriented guidelines. Acknowledgments We would like to acknowledge funding of this project from The National Health and Medical Research Council postgraduate scholarship scheme and the Petre Foundation. BL receives funding from Epilepsy Research United Kingdom (ERUK). We would also like to acknowledge our colleague neurologists for allowing us to describe their cases. Disclosure AV and the Department of Clinical Neurology in Oxford receive royalties and payments for antibody assays, and AV is the named inventor on patent application WO/2010/046716 entitled “Neurological Autoimmune Disorders.” The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC‐complex antibodies. AV and BL are coinventors and may also receive future royalties. None of the other authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Supporting Information References Citing Literature Number of times cited: 39 GenaLynne C. Mooneyham, William Gallentine and Heather Van Mater, Evaluation and Management of Autoimmune Encephalitis, Child and Adolescent Psychiatric Clinics of North America, 10.1016/j.chc.2017.08.011, 27, 1, (37-52), (2018). Crossref John G. Ryder and Jacquelyn M. 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george sperco's curator insight, February 7, 2023 1:32 PM
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Josep Dalmau receives the “Scientific Breakthrough 2023” Award from the American Brain Foundation

The accolade recognises the commitment of this Clínic Barcelona-IDIBAPS researcher to deepening our understanding of autoimmune neurological diseases such...
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IDIBAPS creates three multidisciplinary research programs to encourage collaboration among its groups

They are the Translational cancer research program, the Synaptic autoimmunity in neurology, psychiatry and cognitive neuroscience program and the Lymphoid...
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ExTINGUISH: A Beacon of Hope for NMDAR Encephalitis

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MR Imaging Findings in a Large Population of Autoimmune Encephalitis | American Journal of Neuroradiology

MR Imaging Findings in a Large Population of Autoimmune Encephalitis | American Journal of Neuroradiology | AntiNMDA | Scoop.it
Research ArticleAdult Brain MR Imaging Findings in a Large Population of Autoimmune Encephalitis S. Gillon, M. Chan, J. Chen, E.L. Guterman, X. Wu, C.M. Glastonbury and Y. Li American Journal of Neuroradiology July 2023, 44 (7) 799-806; DOI: https://doi.org/10.3174/ajnr.A7907 ArticleFigures & DataInfo & MetricsReferences PDF This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased. AbstractBACKGROUND AND PURPOSE: Autoimmune encephalitis is a rare condition in which autoantibodies attack neuronal tissue, causing neuropsychiatric disturbances. This study sought to evaluate MR imaging findings associated with subtypes and categories of autoimmune encephalitis.MATERIALS AND METHODS: Cases of autoimmune encephalitis with specific autoantibodies were identified from the medical record (2009–2019). Cases were excluded if no MR imaging of the brain was available, antibodies were associated with demyelinating disease, or >1 concurrent antibody was present. Demographics, CSF profile, antibody subtype and group (group 1 intracellular antigen or group 2 extracellular antigen), and MR imaging features at symptom onset were reviewed. Imaging and clinical features were compared across antibody groups using χ2 and Wilcoxon rank-sum tests.RESULTS: Eighty-five cases of autoimmune encephalitis constituting 16 distinct antibodies were reviewed. The most common antibodies were anti-N-methyl-D-aspartate (n = 41), anti-glutamic acid decarboxylase (n = 7), and anti-voltage-gated potassium channel (n = 6). Eighteen of 85 (21%) were group 1; and 67/85 (79%) were group 2. The median time between MR imaging and antibody diagnosis was 14 days (interquartile range, 4–26 days). MR imaging had normal findings in 33/85 (39%), and 20/33 (61%) patients with normal MRIs had anti-N-methyl-D-aspartate receptor antibodies. Signal abnormality was most common in the limbic system (28/85, 33%); 1/68 (1.5%) had susceptibility artifacts. Brainstem and cerebellar involvement were more common in group 1, while leptomeningeal enhancement was more common in group 2.CONCLUSIONS: Sixty-one percent of patients with autoimmune encephalitis had abnormal brain MR imaging findings at symptom onset, most commonly involving the limbic system. Susceptibility artifact is rare and makes autoimmune encephalitis less likely as a diagnosis. Brainstem and cerebellar involvement were more common in group 1, while leptomeningeal enhancement was more common in group 2.ABBREVIATIONS:AIEautoimmune encephalitisanti-Gq1banti-ganglioside Q1banti-LGI1anti-leucine-rich glioma inactivated 1CASPR2contactin-associated protein-like 2GABAgamma-aminobutyric acidGADglutamic acid decarboxylaseGFAPglial fibrillary acidic proteinNMDAN-methyl-D-aspartatePD-1programmed cell death protein 1VGCCvoltage gated calcium channelVGKCvoltage-gated potassium channel© 2023 by American Journal of NeuroradiologyView Full Text Log in using your username and password Username * Password * Forgot your user name or password? PreviousNext Back to top In this issue American Journal of Neuroradiology Vol. 44, Issue 7 1 Jul 2023 Table of ContentsIndex by authorComplete Issue (PDF) Print Download PDF Email Article Citation Tools Share Tweet WidgetFacebook LikeGoogle Plus One Purchase Related ArticlesNo related articles found.PubMedGoogle Scholar Cited By...No citing articles found.CrossrefGoogle Scholar More in this TOC Section Cost-Effectiveness Analysis of 68Ga-DOTATATE PET/MRI in Radiotherapy Planning in Patients with Intermediate-Risk Meningioma Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study Show more ADULT BRAIN Similar Articles
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Elevated blood and cerebrospinal fluid biomarkers of microglial activation and blood‒brain barrier disruption in anti-NMDA receptor encephalitis | Journal of Neuroinflammation | Full Text

Elevated blood and cerebrospinal fluid biomarkers of microglial activation and blood‒brain barrier disruption in anti-NMDA receptor encephalitis | Journal of Neuroinflammation | Full Text | AntiNMDA | Scoop.it
Background Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the...
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Anti-N-methyl-d-aspartate receptor encephalitis and positive human herpesvirus-7 deoxyribonucleic acid in cerebrospinal fluid: a case report | Journal of Medical Case Reports | Full Text

Anti-N-methyl-d-aspartate receptor encephalitis and positive human herpesvirus-7 deoxyribonucleic acid in cerebrospinal fluid: a case report | Journal of Medical Case Reports | Full Text | AntiNMDA | Scoop.it
Background Anti-N-methyl-d-aspartate receptor encephalitis is a neuroautoimmune syndrome typically presenting with seizures, psychiatric symptoms, and autonomic dysfunction. Human herpesvirus-7 is often found with human herpesvirus-6 and infects leukocytes such as T-cells, monocytes–macrophages,...
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We have a winner! - The Anti-NMDA Receptor Encephalitis Foundation Prize, 2023

We have a winner! - The Anti-NMDA Receptor Encephalitis Foundation Prize, 2023 | AntiNMDA | Scoop.it
It’s that time of year again, when the Foundation is delighted to offer its annual Anti-NMDA Receptor Encephalitis Foundation Prize to a promising neurology trainee ...Read More...
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Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia | Neurology Neuroimmunology & Neuroinflammation

Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
AbstractBackground & Objectives Autoimmune encephalitis (AIE) may present with prominent cognitive disturbances without overt inflammatory changes in MRI and CSF. Identification of these neurodegenerative dementia diagnosis mimics is important because patients generally respond to immunotherapy. The objective of this study was to determine the frequency of neuronal antibodies in patients with presumed neurodegenerative dementia and describe the clinical characteristics of the patients with neuronal antibodies.Methods In this retrospective cohort study, 920 patients were included with neurodegenerative dementia diagnosis from established cohorts at 2 large Dutch academic memory clinics. In total, 1,398 samples were tested (both CSF and serum in 478 patients) using immunohistochemistry (IHC), cell-based assays (CBA), and live hippocampal cell cultures (LN). To ascertain specificity and prevent false positive results, samples had to test positive by at least 2 different research techniques. Clinical data were retrieved from patient files.Results Neuronal antibodies were detected in 7 patients (0.8%), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX, and anti-NMDAR. Clinical symptoms atypical for neurodegenerative diseases were identified in all 7 and included subacute deterioration (n = 3), myoclonus (n = 2), a history of autoimmune disease (n = 2), a fluctuating disease course (n = 1), and epileptic seizures (n = 1). In this cohort, no patients with antibodies fulfilled the criteria for rapidly progressive dementia (RPD), yet a subacute deterioration was reported in 3 patients later in the disease course. Brain MRI of none of the patients demonstrated abnormalities suggestive for AIE. CSF pleocytosis was found in 1 patient, considered as an atypical sign for neurodegenerative diseases. Compared with patients without neuronal antibodies (4 per antibody-positive patient), atypical clinical signs for neurodegenerative diseases were seen more frequently among the patients with antibodies (100% vs 21%, p = 0.0003), especially a subacute deterioration or fluctuating course (57% vs 7%, p = 0.009).Discussion A small, but clinically relevant proportion of patients suspected to have neurodegenerative dementias have neuronal antibodies indicative of AIE and might benefit from immunotherapy. In patients with atypical signs for neurodegenerative diseases, clinicians should consider neuronal antibody testing. Physicians should keep in mind the clinical phenotype and confirmation of positive test results to avoid false positive results and administration of potential harmful therapy for the wrong indication.GlossaryAD=Alzheimer dementia; AIE=autoimmune encephalitis; CBA=cell-based assays; DLB=dementia with Lewy bodies; IHC=immunohistochemistry; LN=live hippocampal cell cultures; PPA=primary progressive aphasia; PSP=progressive supranuclear palsy; RPD=rapidly progressive dementia; VGCC=voltage-gated calcium channelCognitive dysfunction can be the presenting and most prominent symptom in patients with autoimmune encephalitis (AIE).1,2 In contrast to neurodegenerative diseases, patients with antibody-mediated encephalitis might benefit from immunotherapy and improve considerably.3,4 The presence of neuronal antibodies has been reported predominantly in rapidly progressive dementia (RPD).5,6 However, AIE can present less fulminantly and is therefore potentially missed, resulting in diagnosis and treatment delay or even misdiagnosis.7,8 We hypothesized that a small—but not insignificant—part of dementia syndromes is indeed caused by antibody-mediated encephalitis and underdiagnosed, withholding these patients' available treatments. The wish to diagnose every single patient with autoimmune encephalitis is in opposition with the risk for false positive tests.9 Therefore, we strictly adhere to confirmation of positive test results with 2 different test techniques. In this study, we describe the frequency of neuronal antibodies in a cohort of patients diagnosed with various dementia syndromes in a memory clinic. In addition, we present clues to improve clinical recognition of AIE in dementia syndromes.MethodsPatients and Laboratory StudiesIn this retrospective multicenter study, we tested for the presence of neuronal antibodies in serum and CSF samples from patients diagnosed with neurodegenerative dementia diagnosis, included earlier prospectively in established cohorts at 2 large Dutch academic memory clinics (Erasmus University Medical Center, Amsterdam University Medical Centers, location VUmc)10 between 1998 and 2016 (84% last 10 years). All patients fulfilled the core clinical criteria for dementia, as defined by the National Institutes of Aging-Alzheimer Association workgroups.11 Patients were classified into 4 subgroups (based on diagnostic criteria): Alzheimer dementia (AD), frontotemporal dementia (FTD; both behavioral variant and primary progressive aphasia [PPA]), dementia with Lewy bodies (DLB), and other dementia syndromes.11,-,14 Rapidly progressive dementia was defined as dementia within 12 months or death within 2 years after the appearance of the first cognitive symptoms.15 Patients with vascular dementia were not included. Clinic information was retrieved from the prospectively collected data. A subacute deterioration was defined as a marked progression of symptoms in 3 months and a fluctuating course as a disease course fluctuating over a longer period (e.g., weeks to months; different from the fluctuations within a day as seen in some patients with DLB). Dementia markers were scored according to the reference values (per year and per center; included in Table 1).View inline View popup Table 1 Patient Characteristics of Auto-antibody Positive PatientsAll samples, stored in both cohorts' biobanks, were screened for immunoreactivity with immunohistochemistry (IHC), as previously described.16 Preferably, paired serum and CSF were tested for optimal sensitivity and specificity. Samples that were showing a positive or questionable staining pattern were tested more extensively using validated commercial cell-based assays (CBA) and in-house CBA (eTable 1, links.lww.com/NXI/A869). In addition, these samples were tested with live hippocampal cell cultures (LN).16,17 To ascertain specificity, only samples that could be confirmed by CBA or LN were scored as positive because there is a higher risk for false-positive test results in this population with a low a priori chance to have encephalitis.9,18 If IHC was suggestive for antibodies against intracellular (paraneoplastic) targets, this was explored by a different IHC technique.19 Anti-thyroid peroxidase (TPO), voltage-gated calcium channel (VGCC), or low titer glutamic acid decarboxylase antibodies were not tested for because these are generally nonspecific at these ages and are not associated with dementia syndromes.Antibody-positive patients were described exploratory and compared with a randomly selected antibody-negative group (ratio 1:4) matched for memory clinic, dementia subtype, sex, and age (±5 years). For these comparisons, medical records were additionally assessed for both the antibody-positive and antibody-negative patients. All antibody-positive patients were reviewed by a panel consisting of neurologists specialized in neurodegenerative (F.J., H.S., J.S.) or autoimmune diseases (J.V., P.S.S., M.T.), and a consensus classification of AIE vs AIE with a neurodegenerative dementia comorbidity was reached.Statistical AnalysisWe used IBM SPSS 25.0 (SPSS Inc) and Prism 8.4.3 (GraphPad) for statistical analysis. Baseline characteristics were analyzed using the Fisher exact test, the Fisher-Freeman-Halton test, or the Kruskal-Wallis test, when appropriate. For group comparisons, encompassing categorical data, we used the Pearson χ2 test or the Fisher-Freeman-Halton test, when appropriate. Continuous data were analyzed using the Mann-Whitney U test. All p-values were two-sided and considered statistically significant when below 0.05. We applied no correction for multiple testing, and therefore, p values between 0.05 and 0.005 should be interpreted carefully.Standard Protocol Approvals, Registrations, and Patient ConsentsThe study was approved by The Institutional Review Boards of Erasmus University Medical Center Rotterdam and Amsterdam University Medical Center, location VUmc. Written informed consent was obtained from all patients.Data AvailabilityAny data not published within this article are available at the Erasmus MC University Medical Center. Patient-related data will be shared on reasonable request from any qualified investigator, maintaining anonymization of the individual patients.ResultsIn total, 1,398 samples from 920 patients were tested (Figure; in 478, both CSF and serum [52%]). Three-hundred fifty-eight patients were classified as AD (39%), 283 FTD (31%), and 161 DLB (17%). The fourth subgroup with other dementia syndromes consisted of 118 patients (13%), including progressive supranuclear palsy (n = 48, 5%) and corticobasal syndrome (n = 29, 3%). The median age at disease onset was 62 years (range 16–90 years). Male patients were overrepresented (n = 542, 59%), and 60 patients (7%) fulfilled the criteria for rapidly progressive dementia (RPD; eTable 2, links.lww.com/NXI/A869).<img class="highwire-fragment fragment-image" alt="Figure" width="440" height="305" src="https://nn.neurology.org/content/nnn/10/5/e200137/F1.medium.gif">Download figure Open in new tab Download powerpoint Figure Flowchart of Patient Inclusion With Antibody ResultsIn total, 920 patients (1,398 samples) with a presumed neurodegenerative dementia syndrome were tested for the presence of neuronal antibodies in serum and CSF. Neuronal antibodies were detected in 7 patients (0.8%, 95% CI 0.2–1.3); five among the 358 Alzheimer disease patients. Subclassification of the ‘other’ group is provided in supplementary table eTable 2 (links.lww.com/NXI/A869). AD = Alzheimer disease; DLB = diffuse Lewy body dementia; DPPX = dipeptidyl aminopeptidase-like protein 6; FTD = frontotemporal dementia; IgLON5 = Ig-like domain-containing protein family member 5; LGI1 = leucin-rich glioma inactivated protein 1; NMDAR = N-methyl-d-aspartate receptor; S = serum.Neuronal antibodies were detected in 7 patients (0.8%; 5 in the AD group: 1.4%; Figure), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX (n = 1), and anti-NMDAR antibodies (n = 1; Table 1). Among these 7, 4 patients were diagnosed retrospectively with an exclusive diagnosis of AIE, while 3 patients were classified to have AIE (anti-IgLON5 [n = 2] and anti-NMDAR antibodies [n = 1]) with a neurodegenerative dementia comorbidity. No patients with antibodies fulfilled the criteria for RPD, yet a subacute deterioration later in the disease was reported in 3 patients. Atypical clinical signs for neurodegenerative diseases were present in 7 of 7 antibody-positive patients (100% vs 21% in antibody-negative patients, p = 0.0003; Table 2). These included a subacute deterioration (n = 3), myoclonus (n = 2), a fluctuating disease course over months (n = 1), a history of autoimmune disease (n = 2), and epileptic seizures (n = 1; Table 1). Brain MRI of none of the patients demonstrated abnormalities suggestive for active AIE, in particular no hippocampal swelling nor increased T2-signal intensity. CSF pleocytosis was found in 1 patient. CSF biomarkers (t-tau, p-tau, and Aβ42) were tested in 5 of 7 patients, and t-tau and p-tau were increased in 4, while a low Aβ42 was seen in 2. Of note, only 1 patient had the combination of reduced Aβ42 and increased p-tau/t-tau, and was diagnosed with a comorbid AD. No patient received immunotherapy. Two patients still alive (1 anti-LG1, 1 anti-DPPX positive) were contacted but refused to visit our clinic to try very delayed immunotherapy trials. It is of interest that the patient with anti-DPPX antibodies showed spontaneous improvement of cognitive disturbances, atypical for a pure neurodegenerative disease.View inline View popup Table 2 Comparisons Between Patients With Neuronal Auto-antibodies and Antibody-Negative PatientsCompared with the patients without neuronal antibodies, subacute cognitive deterioration or fluctuating course was present more frequently (4/7 [57%] vs 2/28 [7%], p = 0.009). Although movement disorders (myoclonus) and autoimmune disorders were present in 2 of 7 patients each, this did not reach significance (Table 2).DiscussionIn this large, multicenter, cohort study consisting of patients with a presumed neurodegenerative dementia diagnosis, we show that a small, but clinically relevant proportion (0.8%) have neuronal antibodies. In this particular group, 4 of 7 antibody-positive patients presented with an atypical clinical course (subacute deterioration or fluctuating disease course), which is considered as a clinical clue (‘red flag’) for an antibody-mediated etiology of dementia.4 It is important that a fluctuating disease course was observed over a longer period (e.g., weeks or months) in AIE and should not be confused with shorter fluctuations of cognition or alertness (over the day) in DLB. Other known red flags, which we observed in these 7 patients, were myoclonus, epilepsy, pleocytosis, or a history of autoimmune disorders, as described earlier.1,4,-,6 Compared with antibody-negative patients, no significant difference was found related to these symptoms alone, probably due to the low number of positive patients and related low power. However, atypical clinical signs for neurodegenerative diseases together were seen significantly more frequently in the antibody-positive group. Within this cohort mostly devoid of patients with RPD, none of the antibody-positive patients fulfilled the criteria for RPD, nor ancillary testing showed specific signs for AIE in most patients. This implicates that AIE can resemble more protracted, progressive neurodegenerative dementia syndromes, as we reported earlier.1Three antibody-positive patients had IgLON5 antibodies, which is a very rare and known to have heterogeneous (chronic) clinical manifestations, including pronounced sleep problems, cognitive dysfunction, and movement disorders.20,21 Misdiagnosis with progressive supranuclear palsy (PSP) is reported, mainly associated with the preceding movement disorders. In addition, half of the patients have cognitive impairment of whom 20% fulfilled clinical criteria for dementia.21 It is of interest that IgLON5 disease shares features with neurodegeneration because autopsy studies showed tau deposits.22 However, there is a strong HLA association,20 and studies show that antibodies directly bind to surface IgLON5 on neurons and directly alter neuronal function and structure,23 suggesting a primary inflammatory disease.In previous research, a notably higher frequency (14%) of neuronal antibodies in patients with dementia was reported by Giannocaro et al.24 The discrepancy with our test results is probably explained by differences in patient selection and antibody testing methodology. First, 30% of the patients in the cohort described by Giannocaro et al. demonstrated CSF inflammatory abnormalities, indicating a relatively high pretest probability of antibody-positivity compared with our study.24 A lack of CSF pleocytosis probably better represents the population of memory clinics. Second, the previous study exclusively tested serum by cell-based assay without confirmatory tests nor testing antibodies in CSF.24 We only considered antibody test results positive when confirmed by additional techniques to avoid suboptimal specificity and false-positive test results.9Previous studies, including our own, suggested RPD as a relevant red flag for AIE,1,4,9,25 but we cannot determine this from our study based on the design of our study. We included patients at tertiary memory clinics without overt signs or symptoms suggestive for encephalitis. Therefore, the amount of patients with RPD included was very limited (7%), comparable with other large dementia cohort studies, as was the amount of patients with abnormal ancillary testing suggestive for AIE because this would have prompted a different approach than referral to a tertiary memory clinic. These patients with RPD and ancillary testing suggestive of AIE were not included in our study. Inclusion of those patients would have likely increased our rate of positivity.The strength of our study is the large number of paired samples (serum and CSF combined) from a cohort with various presumed neurodegenerative diseases without AIE suspicion, representative for academic memory clinics. A limitation is the lack of neuropathologic data to support our findings and make diagnoses of neurodegeneration or inflammation definite. To confirm if the symptoms are related to the presence of antibodies, we tried to overcome this concern in different ways. First, the presence of antibodies in serum and CSF was confirmed by different techniques (cell-based assay, tissue immunohistochemistry, and cultured live neurons), indicating optimal test specificity. Second, afterward patients were thoroughly reviewed by a panel of neurologists specialized in neurodegenerative or autoimmune disease to detect atypical signs and symptoms related to AIE. This is a very large cohort of patients with dementia examined for the presence of neuronal antibodies. Nevertheless, an important limitation of this study is the small number of antibody-positive patients, underpowering the probability to identify significant differences between antibody-positive and antibody-negative patients. The low number of patients with RPD has probably added to this small number, and a prospective study including patients with RPD is recommended. Nevertheless, several probable red flags could be identified. Diagnosing AIE in patients with dementia is highly relevant because these patients might respond to immunotherapy. Therefore, clinicians should test for neuronal antibody in patients demonstrating red flags suggestive for an autoimmune etiology, if possible early in disease course. When profound temporal lobe atrophy already has developed, little effect is to be expected. Red flags identified in this study are subacute deterioration or fluctuating course. Other red flags described previously, we also see reflected in our study, are autoimmune disorders, myoclonus, seizures, and pleocytosis,1,4,-,6 Preferably, both serum and CSF should be tested and confirmed by additional techniques. Always consider the possibility of a false positive test result, especially when only using a single technique (like the commercial cell-based assay). If the clinical phenotype is atypical, confirmation in a research laboratory should be mandatory. The use of antibody panels is discouraged, especially including the paraneoplastic blots, because these are associated with higher risks of lack of clinical relevance.26 This caution is even more warranted for tests not associated with neurodegenerative syndromes, but with a history of nonspecificity, including VGKC (in the absence of LGI1 or CASPR2), VGCC, anti-TPO, and low-titer anti-GAD65.27,-,30 Further research should focus on improving clinical recognition of AIE in patients with dementia determining the effect of immunotherapy in this specific patient category and assessing the frequency of AIE in RPD.In conclusion, we have shown that a clinically relevant, albeit small proportion of patients with a suspected neurodegenerative disease and nonrapidly progressive course have neuronal antibodies indicative of AIE.Study FundingM.J. Titulaer was supported by an Erasmus MC fellowship and has received funding from the Netherlands Organization for Scientific Research (NWO, Veni incentive), ZonMw (Memorabel program), the Dutch Epilepsy Foundation (NEF 14-19 & 19-08), Dioraphte (2001 0403), and E-RARE JTC 2018 (UltraAIE, 90030376505). F. Leypoldt has received funding from the German Ministry of Education and Research (01GM1908A) and the Era-Net funding program (LE3064/2-1).DisclosureA.E.M. Bastiaansen reports no disclosures. R.W. van Steenhoven reports no disclosures. Research programs of Wiesje van der Flier have been funded by ZonMW, now, EUFP7, EU-JPND, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, and Combinostics. W.M. van der Flier holds the Pasman chair. W.M. van der Flier is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). All funding is paid to her institution. WF has performed contract research for Biogen MA Inc and Boehringer Ingelheim. All funding is paid to her institution. W.M. van der Flier has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), and Springer Healthcare. All funding is paid to her institution. W.M. van der Flier is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. All funding is paid to her institution. W.M. van der Flier participated in advisory boards of Biogen MA Inc and Roche. All funding is paid to her institution. W.M. van der Flier is a member of the steering committee of PAVE and Think Brain Health. W.M. van der Flier was an associate editor of Alzheimer, Research & Therapy in 2020/2021. W.M. van der Flier is an associate editor at Brain. Research of C. Teunissen was supported by the European Commission (Marie Curie International Training Network, Grant Agreement No. 860197 (MIRIADE)), Innovative Medicines Initiatives 3TR (Horizon 2020, Grant No. 831434), EPND (IMI 2 Joint Undertaking (JU) under Grant Agreement No. 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance) and Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, and Alzheimer Association. C. Teunissen is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP-allowance, #LSHM20106). ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. C. Teunissen has a collaboration contract with ADx Neurosciences, Quanterix, and Eli Lilly, performed contract research or received grants from AC-Immune, Axon Neurosciences, Bioconnect, Bioorchestra, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, Grifols, Novo Nordisk, PeopleBio, Roche, Toyama, and Vivoryon. She serves on editorial boards of Medidact Neurologie/Springer, Alzheimer Research and Therapy, and Neurology: Neuroimmunology & Neuroinflammation and is an editor of a Neuromethods book Springer. She had speaker contracts for Roche, Grifols, and Novo Nordisk. E. de Graaff holds a patent for the detection of anti-DNER antibodies. M.M.P. Nagtzaam reports no disclosures. M. Paunovic reports no disclosures. S. Franken reports no disclosures. M.W.J. Schreurs reports no disclosures. F. Leypoldt has received speakers honoraria from Grifols, Roche, Novartis, Alexion, and Biogen and serves on an advisory board for Roche and Biogen. He works for an academic institution (University Hospital Schleswig-Holstein) which offers commercial autoantibody testing. P.A.E. Sillevis Smitt holds a patent for the detection of anti-DNER and received research support from Euroimmun. J.M. de Vries reports no disclosures. H. Seelaar reports no disclosures. J.C. van Swieten reports no disclosures. F.J. de Jong reports no disclosures. Y.A.L. Pijnenburg Research of Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The chair of Wiesje van der Flier is supported by the Pasman stichting. M.J. Titulaer has filed a patent, on behalf of the Erasmus MC, for methods for typing neurologic disorders and cancer, and devices for use therein, and has received research funds for serving on a scientific advisory board of Horizon Therapeutics, for consultation at Guidepoint Global LLC, for consultation at UCB, for teaching colleagues by Novartis. MT has received an unrestricted research grant from Euroimmun AG and from CSL Behring. Go to Neurology.org/NN for full disclosure.AcknowledgmentThe authors thank all patients for their participation. The authors also thank Esther Hulsenboom and Ashraf Jozefzoon-Aghai for their technical assistance. M.W.J. Schreurs, F. Leypoldt, P.A.E. Sillevis Smitt, J.M. de Vries, and M.J. Titulaer of this publication are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory, and Autoimmune Diseases—Project ID No. 739543 (ERN-RITA; HCP Erasmus MC and University Hospital Schleswig-Holstein). H. Seelaar, J.C. van Swieten, and F.J. de Jong of this publication are members of the European Reference Network for Rare Neurological Diseases—Project ID 73910. Research of the VUmc Alzheimer center is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center VUmc is supported by Alzheimer Nederland and Stichting VUmc Fonds. The clinical database structure was developed with funding from Stichting Dioraphte.Appendix Authors<img class="highwire-fragment fragment-image" alt="Table" src="https://nn.neurology.org/content/nnn/10/5/e200137/T3.medium.gif"; width="599" height="2531">FootnotesGo to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.The Article Processing Charge was funded the authors.Submitted and externally peer reviewed. The handling editor was Editor Josep O. Dalmau, MD, PhD, FAAN.Received December 8, 2022.Accepted in final form May 8, 2023.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.References1.↵Bastiaansen AEM, van Steenhoven RW, de Bruijn M, et al. Autoimmune encephalitis resembling dementia syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1039.OpenUrlAbstract/FREE Full Text2.↵Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol. 2010;9(1):67-76.OpenUrlCrossRefPubMed3.↵Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12(2):157-165.OpenUrlCrossRefPubMed4.↵Flanagan EP, McKeon A, Lennon VA, et al. Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc. 2010;85(10):881-897.OpenUrlCrossRefPubMed5.↵Geschwind MD, Tan KM, Lennon VA, et al. Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease. Arch Neurol. 2008;65(10):1341-1346.OpenUrlCrossRefPubMed6.↵Grau-Rivera O, Sanchez-Valle R, Saiz A, et al. Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease. JAMA Neurol. 2014;71(1):74-78.OpenUrl7.↵Titulaer MJ, McCracken L, Gabilondo I, et al. Late-onset anti-NMDA receptor encephalitis. Neurology. 2013;81(12):1058-1063.OpenUrlAbstract/FREE Full Text8.↵Gaig C, Graus F, Compta Y, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology. 2017;88(18):1736-1743.OpenUrlAbstract/FREE Full Text9.↵Bastiaansen AEM, de Bruijn M, Schuller SL, et al. Anti-NMDAR encephalitis in The Netherlands, focusing on late-onset patients and antibody test accuracy. Neurol Neuroimmunol Neuroinflamm. 2022;9(2):e1127.OpenUrl10.↵van der Flier WM, Scheltens P. Amsterdam dementia cohort: performing research to optimize care. J Alzheimers Dis. 2018;62(3):1091-1111.OpenUrl11.↵McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-269.OpenUrlCrossRefPubMed12.↵Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456-2477.OpenUrlCrossRefPubMed13.↵Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014.OpenUrlAbstract/FREE Full Text14.↵McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88-100.OpenUrlAbstract/FREE Full Text15.↵Geschwind MD. Rapidly progressive dementia. Continuum (Minneap Minn). 2016;22(2 Dementia):510-537.OpenUrl16.↵Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 2005;128(Pt 8):1764-1777.OpenUrlCrossRefPubMed17.↵Gresa-Arribas N, Titulaer MJ, Torrents A, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13(2):167-177.OpenUrlCrossRefPubMed18.↵Martinez-Martinez P, Titulaer MJ. Autoimmune psychosis. Lancet Psychiatry. 2020;7(2):122-123.OpenUrl19.↵van Coevorden-Hameete MH, Titulaer MJ, Schreurs MW, et al. Detection and characterization of autoantibodies to neuronal cell-surface antigens in the central nervous system. Front Mol Neurosci. 2016;9:37.OpenUrl20.↵Sabater L, Gaig C, Gelpi E, et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol. 2014;13(6):575-586.OpenUrlCrossRefPubMed21.↵Gaig C, Compta Y, Heidbreder A, et al. Frequency and characterization of movement disorders in anti-IgLON5 disease. Neurology. 2021;97(14):e1367–e1381.OpenUrlAbstract/FREE Full Text22.↵Gelpi E, Hoftberger R, Graus F, et al. Neuropathological criteria of anti-IgLON5-related tauopathy. Acta Neuropathol. 2016;132(4):531-543.OpenUrlCrossRefPubMed23.↵Landa J, Gaig C, Plaguma J, et al. Effects of IgLON5 antibodies on neuronal cytoskeleton: a link between autoimmunity and neurodegeneration. Ann Neurol. 2020;88(5):1023-1027.OpenUrlCrossRefPubMed24.↵Giannoccaro MP, Gastaldi M, Rizzo G, et al. Antibodies to neuronal surface antigens in patients with a clinical diagnosis of neurodegenerative disorder. Brain Behav Immun. 2021;96:106-112.OpenUrl25.↵Hermann P, Zerr I. Rapidly progressive dementias - aetiologies, diagnosis and management. Nat Rev Neurol. 2022;18(6):363-376.OpenUrl26.↵Dechelotte B, Muniz-Castrillo S, Joubert B, et al. Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e701.OpenUrlAbstract/FREE Full Text27.↵van Sonderen A, Schreurs MW, de Bruijn MA, et al. The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology. 2016;86(18):1692-1699.OpenUrlCrossRefPubMed28.↵Muñoz Lopetegi A, Boukhrissi S, Bastiaansen A, et al. Neurological syndromes related to anti-GAD65: clinical and serological response to treatment. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e696.OpenUrlAbstract/FREE Full Text29.↵Mattozzi S, Sabater L, Escudero D, et al. Hashimoto encephalopathy in the 21st century. Neurology. 2020;94(2):e217-e224.OpenUrlAbstract/FREE Full Text30.↵Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80(1):30-39.OpenUrl
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Research study - can you help?

Research study - can you help? | AntiNMDA | Scoop.it
Researchers at Kings College London are looking for young people to travel to London and help with an encephalitis study...
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Sociocultural Influences in Autoimmune Encephalitis Without Neurologic Symptoms

Sociocultural Influences in Autoimmune Encephalitis Without Neurologic Symptoms | AntiNMDA | Scoop.it
This complex case highlights barriers to identifying autoimmune encephalitis when no neurologic symptoms are present, which are normally central to disease detection.
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Anti N-Methyl-D-Aspartate receptor antibody associated Acute Demyelinating Encephalomyelitis in a patient with COVID-19: a case report | Journal of Medical Case Reports | Full Text

Anti N-Methyl-D-Aspartate receptor antibody associated Acute Demyelinating Encephalomyelitis in a patient with COVID-19: a case report | Journal of Medical Case Reports | Full Text | AntiNMDA | Scoop.it
Background Anti N-Methyl-D-Aspartate (NMDA) receptor antibody associated ADEM is a diagnosis that was first described relatively recently in 2007 by Dalmau et al. The recent COVID-19 pandemic has resulted in multiple neurological complications being reported.
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Autoimmune Encephalitis Consensus Criteria | Neurology Clinical Practice

Autoimmune Encephalitis Consensus Criteria | Neurology Clinical Practice | AntiNMDA | Scoop.it
June 2023; 13 (3) Editorial Autoimmune Encephalitis Consensus CriteriaLessons Learned From Real-World Practice View ORCID ProfileJeffrey M. Gelfand, Chu-Yueh Guo First published April 25, 2023, DOI: https://doi.org/10.1212/CPJ.0000000000200155 Full PDF Citation Permissions Make Comment See Comments Downloads133 Share Article Info & Disclosures This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased. Autoimmune encephalitis (AE) encompasses a spectrum of neurologic disorders caused by brain inflammation, a subset of which is associated with autoantibodies to neuronal cell-surface antigens such as anti-N-methyl-d-aspartate (NMDA) receptor AE or anti-leucine-rich glioma-inactivated 1 (LGI1) AE.1 Up to half of patients with AE, however, do not have abnormal neuronal or glial autoantibodies identified and are classified as having “seronegative” AE.2 Clinical antibody testing can take several days to result, a time in which clinicians caring for patients with suspected AE may wish to initiate empiric immunosuppressive therapy. Antibody testing is also not readily accessible in some health care settings and, even when technically available, may require time-consuming advocacy with local clinical laboratories to justify relatively costly send-out testing. To add further complexity, some patients with immunoreactive (e.g., laboratory true-positive) antibodies do not have clinical AE, and over-reliance and misapplication of antibody testing were identified as important contributors to AE misdiagnosis in a 2023 multicenter analysis.3FootnotesFunding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.See page e200151© 2023 American Academy of NeurologyView Full Text AAN Members We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page. Google Safari Microsoft Edge Firefox Click here to login AAN Non-Member Subscribers Click here to login Purchase access For assistance, please contact: AAN Members (800) 879-1960 or (612) 928-6000 (International) Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international) Sign Up Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here Purchase Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed. You May Also be Interested in Back to top Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials Dr. Nicole Sur and Dr. Mausaminben Hathidara ► Watch Related Articles Autoimmune Encephalitis Criteria in Clinical Practice Topics Discussed All Clinical Neurology Autoimmune diseases Encephalitis Alert Me Alert me when eletters are published
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Predictive Value of Serum Neurofilament Light Chain Levels in Anti-NMDA Receptor Encephalitis

Predictive Value of Serum Neurofilament Light Chain Levels in Anti-NMDA Receptor Encephalitis | AntiNMDA | Scoop.it
Increased serum NfL levels reflect neuroaxonal damage in anti-NMDAR encephalitis. No relationship was identified with disease severity, whereas the association with outcome was confounded by age.The implied role of sampling timing on NfL levels also limits the applicability of NfL as a prognostic...
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Frontiers | The MOG antibody associated encephalitis preceded by COVID-19 infection; a case study and systematic review of the literature

Frontiers | The MOG antibody associated encephalitis preceded by COVID-19 infection; a case study and systematic review of the literature | AntiNMDA | Scoop.it
BackgroundNew neurological complications of COVID-19 infection have been reported in recent research. Among them, the spectrum of anti-MOG positive diseases, defined as anti-MOG antibody associated disease (MOGAD), is distinguished, which can manifest as optic neuritis, myelitis, or various forms...
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Enceph-IG Study - Institute of Infection, Veterinary and Ecological Sciences - University of Liverpool

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A Rare Presentation of Steroid-responsive Encephalopathy Associated with Autoimmune Thyroiditis with Neuropsychiatric Symptoms: A Case Report

A Rare Presentation of Steroid-responsive Encephalopathy Associated with Autoimmune Thyroiditis with Neuropsychiatric Symptoms: A Case Report | AntiNMDA | Scoop.it
A 42-year-old woman presented in the emergency department with acute onset whole-body myoclonic jerks for 1 day.On enquiry, the patient’s parents advised...
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Pioneering Research in Autoimmune Neurology: Vanda Lennon, M.D., Ph.D.

Pioneering Research in Autoimmune Neurology: Vanda Lennon, M.D., Ph.D. | AntiNMDA | Scoop.it
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New center to spotlight neurological autoimmune disorders

New center to spotlight neurological autoimmune disorders | AntiNMDA | Scoop.it
How do neurological disorders arise that are caused, triggered, or influenced by antibodies? What better possibilities are there for diagnosis – and above all for treatment? These are the questions addressed by the new Clinical Research Unit “BecauseY” headed by Charité – Universitätsmedizin Berlin.
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Progressive alliance advances science through patient-powered research

Progressive alliance advances science through patient-powered research | AntiNMDA | Scoop.it
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ENCEPH-IG Trial: The Challenges Of Running A Rare Disease Trial - Centre for Trials Research

ENCEPH-IG Trial: The Challenges Of Running A Rare Disease Trial - Centre for Trials Research | AntiNMDA | Scoop.it
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30 neurological disorders every doctor should know about –

30 neurological disorders every doctor should know about – | AntiNMDA | Scoop.it
Neurology is a jungle of disorders and syndromes. This creates a challenge for doctors and medical students... What to prioritise for learning and practice? *** To solve this conundrum... We combed the extensive database of Neurochecklists...
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A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis

A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis | AntiNMDA | Scoop.it
The NEOS score accurately predicts 1-year functional status in patients with anti-NMDAR encephalitis. This score could help estimate the clinical course following diagnosis and may aid in identifying patients who could benefit from novel therapies.
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Canadian Blood Services needs thousands more donors to roll up their sleeves | CBC News

Canadian Blood Services needs thousands more donors to roll up their sleeves | CBC News | AntiNMDA | Scoop.it
Canadian Blood Services is looking to fill 150,000 appointments for people willing to donate their blood or plasma to tackle a shortage.
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A catatonic woman awakened after 20 years. Her story may change psychiatry – My Health CRM

A catatonic woman awakened after 20 years. Her story may change psychiatry – My Health CRM | AntiNMDA | Scoop.it
New research suggests that a subset of patients with psychiatric conditions such as schizophrenia may actually have autoimmune disease that attacks the brain...
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Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases

Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases | AntiNMDA | Scoop.it
Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders...
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Medical Moment: The signs of ‘brain-on-fire’ disease

Medical Moment: The signs of ‘brain-on-fire’ disease | AntiNMDA | Scoop.it
(WNDU) - Imagine being totally fine one day, then the next, you’re having hallucinations, seizures, memory loss, and even trouble talking.It’s called “brain-on-fire” disease or anti-NMDA receptor encephalitis. It’s a rare neurological disorder that can cause inflammation in the brain.It occurs when the body’s immune system mistakenly attacks the NMDA receptors in the brain, which are responsible for regulating communication between nerve cells. Brain-on-fire disease is often misdiagnosed as other neurological disorders or psychiatric illnesses because its symptoms are similar to those of many other conditions.However, a blood or cerebrospinal fluid test can help diagnose the disease by detecting the presence of antibodies that attack the NMDA receptors in the brain. The disease is rare as it affects one in 1.5 million people a year.Katie Miller would be one of those people.Hunting, mountain biking, horseback riding - you name it, Katie Miler would do it... until she couldn’t.“I just didn’t feel like myself, like normal,” Katie recalled.“Katie said, ‘Mom, I feel like my brain snapped,’” said Colleen Miller, Katie’s mother.Local doctors admitted Katie into a psychiatric ward, but what was happening to Katie wasn’t mental; it was physical.“What happens is you’re perfectly normal one day, and suddenly overnight, this person can become paranoid, can start having visual hallucinations, auditory hallucinations,” explained Stacy Clardy, MD, PhD, an autoimmune neurologist at the University of Utah.Anti-NMDA receptor encephalitis is misdiagnosed as a psychiatric disorder in up to 40% of patients.“So, for many of the females, especially after puberty, they can develop what’s called an ovarian dermoid cyst or an ovarian teratoma,” Dr. Clardy said.These cysts often have hair and teeth in them. The immune system sees it as foreign and attacks it, but...“In these cysts, there is a component of tissue that really is brain tissue,” Dr. Clardy continued.Within four days, Katie was catatonic and needed a ventilator to breathe. There is no single approved treatment. That’s why a five-year, nationwide clinical trial is testing whether a drug called Inebilizumab will stop the assault on the brain. It has the potential to improve outcomes for patients who are not responding to other treatments and may also lead to fewer long-term neurological effects.Katie had her cyst removed; she can’t remember three months of her life. But now, with various medications, Katie is on her way to recovery.Up to 50% of patients can suffer long-term consequences, especially cognitive and mood symptoms.Copyright 2023 WNDU. All rights reserved.
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