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Autoimmune Neurology | Neurology Neuroimmunology & Neuroinflammation

Autoimmune Neurology | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
From nn.neurology.org - June 17, 2021 11:18 PM
Abstract Autoimmune neurology is a rapidly developing specialty driven by an increasing recognition of autoimmunity as the cause for a broad set of neurologic disorders and ongoing discovery of new neural autoantibodies associated with recognizable clinical syndromes. The diversity of clinical presentations, unique pathophysiology, and the complexity of available treatments requires a dedicated multidisciplinary team to diagnose and manage patients. In this article, we focus on antibody-associated autoimmune encephalitis (AE) to illustrate broader themes applicable to the specialty. We discuss common diagnostic challenges including the utilization of clinical assessment tools along with the determination of the prognostic significance of certain autoantibodies, with a focus on implications for long-term management. A growing body of literature demonstrates the long-term cognitive, behavioral, and physical sequelae of AE. Dedicated resources are needed to effectively manage these patients. These resources may be best provided by experienced neurology clinics in partnership with other neurologic subspecialists, as well as psychiatrists, neuropsychologists, and physical medicine and rehabilitation providers. Glossary AE=autoimmune encephalitis; AED=antiepileptic drug; CASE=Clinical Assessment Scale in Autoimmune Encephalitis; ICU=intensive care unit; LGI-1=leucine-rich, glioma-inactivated 1; mRS=modified Rankin Scale; NEOS=NMDAR Encephalitis One-Year Functional Status; NMDAR=NMDA receptor Over the past 2 decades, there has been rapid growth in the discovery of antibody-associated neurologic diseases. Autoantibodies that target neural antigens lead to a diverse phenotype of neurologic diseases. Diagnosing and managing neurologic autoantibody-associated disorders is challenging and requires a thoughtful approach. The spectrum of symptoms associated with these autoantibodies is vast—involving central, peripheral, and autonomic nervous systems—with contributors to disease encompassing paraneoplastic, parainfectious, immunotherapy-induced, and “unknown” (i.e., cryptogenic) causes.1,-,3 In this article, we not only explore common challenges in the initial diagnosis but also discuss the importance of long-term, comprehensive outpatient management of patients with antibody-associated autoimmune encephalitis (AE). In the acute setting, we focus on common challenges faced in the hospital while offering a perspective on potential prognostic tools. A comprehensive approach to care is proposed, emphasizing the need for multidisciplinary care led by a neurologist with experience in managing autoimmune neurologic disorders to mitigate the long-term physical and psychosocial devastation associated with these illnesses.4,-,6 We focus on adult-onset AE, as it is one of the most common antibody-associated neurologic disorders and has a robust array of literature to offer an evidence-based discussion. However, our themes apply broadly to other autoimmune neurologic disorders, including those involving the peripheral and autonomic nervous systems. Initial Diagnosis AE can produce a diverse set of symptoms that usually comprises both limbic and extralimbic dysfunction including impaired cognition and short-term memory, psychiatric symptoms, focal neurologic deficits, and altered level of consciousness. Patients may initially present to clinicians outside of neurology, such as psychiatry or internal medicine, which can delay prompt diagnosis and treatment.7,8 In 1 multisite study, AE was initially suspected in only 32% of patients despite 80% of patients presenting with symptoms and signs typical of an immune-mediated neurologic disorder.9 Even in tertiary care centers, there can be significant delays in diagnosis, contributing to delays in treatment and prolongation of hospital stay.10 Recognition of characteristic clinical syndromes is critical given the potential reversibility of these disorders. Clinical consensus criteria for AE, published in 2016,11 can help with this, offering objective measures to anchor the AE diagnosis. These criteria prioritized findings on clinical history and examination, in combination with the results of commonly available tests, with the goal of promoting early recognition and treatment independent of autoantibody test results. Autoantibody testing should still be obtained, recognizing that the identification of specific disease–associated autoantibodies may establish the diagnosis of definite AE, dictate the risk of underlying malignancy, guide treatment decisions, and inform long-term prognosis, including the risk of relapse. When possible, serum and CSF should be tested for autoantibodies because the sensitivity of commercially available antibody tests can be more sensitive in CSF (i.e., NMDA receptor [NMDAR] encephalitis12) and serum for others (i.e., leucine-rich, glioma-inactivated 1 [LGI-1] encephalitis13). Comprehensive but targeted autoantibody evaluations are usually preferred over single, specific autoantibody tests given the potential overlapping clinical syndromes, and the clinical significance assigned to the identification of more than 1 antibody.14 Clinicians should also be aware that a low titer result may also accompany other pathologically relevant results. In addition, the specificity and sensitivity can vary for different antibodies (table), so clinicians need to understand the diagnostic limitations of some autoantibody panels. View inline View popup Table Autoantibody Test Results That Need to Be Interpreted Cautiously Subtle or atypical presentations of AE may be more challenging to recognize, including LGI-1 antibody encephalitis, which may manifest with subacute cognitive decline.15 Certain subpopulations such as pediatric or geriatric cohorts may also pose challenges. Recent studies have shown that older patients (usually defined as 60 years or older) may have an immune-mediated disorder without evidence for CNS inflammation.16 Evaluating for other systemic findings such as gastrointestinal symptoms or progressive sleep dysfunction may be the only diagnostic clue in patients presenting with subacute cognitive decline.16 Subtle clues on diagnostic testing such as unique CSF oligoclonal bands may also be central to the diagnosis.17 A comprehensive review of established antibody-mediated disorders is beyond the scope of this article but well covered in other sources.7,18 Acute Prognosis and Treatment Patients with AE need specialized care. Most cases are likely to require advanced diagnostic imaging and treatment by specially trained clinicians with AE experience. Complex patients may require intensive care unit (ICU) management for complications including hypoventilation, bradycardia, severe blood pressure changes, encephalopathy (with failure to protect the airway), seizures (with or without status epilepticus), and severe movement disorders, including potential neuroleptic malignant syndrome. Patients with NMDAR encephalitis are at an especially high risk of autonomic dysfunction, requiring close monitoring (figure 1). Patients with AE have also been reported to have a higher rate of severe sepsis and shock when compared with the general ICU population.19 Figure 1 Typical Clinical Course Associated With Anti-NMDAR Encephalitis ICU = intensive care unit; IVMP = IV methylprednisolone; mRS = modified Rankin Scale; NEOS = NMDAR Encephalitis One-Year Functional Status; NMDAR = anti-NMDA receptor. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2021. All Rights Reserved. Providers with experience in managing AE can offer important guidance to avoid undertreatment or overtreatment, thereby avoiding the risk for complications. For example, differentiating seizure-related activity from dyskinetic or stereotypic movements is essential, as unnecessary administration of antiepileptic drugs (AEDs) could prolong recovery. Likewise, an understanding of the time to efficacy of commonly administered immunomodulatory treatments can prevent side effects associated with excessive immunosuppression. Recommendations governing the acute treatment in AE are derived from expert opinion, case series, and case reports. Current data suggest that early initiation of commonly available therapies—namely, high-dose steroids and IV immunoglobulin or plasma exchange—and timely escalation to second-line immunotherapy may lead to improved clinical outcomes, although randomized controlled trials are needed to inform optimal treatment approaches.4,20 Detailed knowledge of individual prognostic factors is essential to accurately inform decision making. Consultation with a neurologist with experience in AE can help outline the typical timeline and prognosis for recovery, which can provide context for families and caregivers alike. A multicenter AE ICU cohort study conducted in Germany illustrated that despite the severity of the disease, the majority experienced significant recovery before discharge.21 Thus, it is imperative that clinicians are patient in the course of AE recovery, as improvement can be delayed and may not directly correlate with laboratory or imaging findings. The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score was developed as a more specialized alternative to the modified Rankin Scale (mRS), which has been historically used as an outcome measure in retrospective AE studies. This score is based on 9 items—seizure, memory dysfunction, psychiatric symptoms, consciousness, language difficulties, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and motor weakness—with higher scores corresponding to greater severity of illness. This scale helps to overcome some of the current limitations in the initial assessment of AE, but more studies are needed to determine whether treatment decisions should be made in response to scores and scores relate to long-term outcomes.22 Given the slow and variable trajectory in recovery, the NMDAR Encephalitis One-Year Functional Status (NEOS) score was created to predict functional status for patients (figure 1). This 5-point score predicts an mRS at ≥3 at 1 year based on ICU admission, treatment delay by >4 weeks, lack of clinical improvement after 4 weeks of treatment, abnormal brain MRI, and a significant CSF pleocytosis (>20 cells/μL). This score could help identify patients who may benefit from more aggressive or longer duration immunotherapy or from novel therapies. This study also reaffirmed that patients with a high NEOS score can still achieve function independence even 2 years after the initial diagnosis.5 Prospective validation of both the CASE and NEOS in a variety of populations will further strengthen confidence in these encephalitis-specific instruments and allow multidisciplinary teams to appropriately allocate resources after discharge to achieve optimal outcomes. Care Coordination and Discharge Planning Targeted interventions at the time of discharge can improve patient outcomes, reduce burden on family members, and decrease hospital readmissions. Ideally, interventions should include adequate education for family members and caregivers. It is also vital to consider the perspective of caregivers, recognizing the potential contributions of caregiver mental and physical health, coping strategies, and access to resources to patient outcomes. These individuals are integral players in patients' recovery but also have their own physical and psychological needs.23 A national survey through the Encephalitis Society and the Autoimmune Encephalitis Alliance found communication and expectations for caregivers to be lacking—a finding that was associated with higher levels of caregiver burden. In particular, poor transition from the inpatient to outpatient setting was a strong factor for higher levels of burden and highlighted the need for a comprehensive follow-up in a neurology clinic.23 It is important to identify patients in the hospital setting to ensure proper follow-up. In our experience, specialty referrals often occur late, including after hospital discharge. This potentially leaves patients undertreated while being sent home or to a rehabilitation prematurely or without sufficient care plans in place. Our proposed clinic model allows for timely referrals especially as patients are transitioned from the inpatient service while also offering treatment and surveillance of suspected and confirmed AE cases. We typically arrange for close follow-up (e.g., every 3–4 months) at the time of diagnosis or hospital discharge. These follow-up appointments can be extended if patients remain stable to every 6–12 months, although these decisions must be made in the context of individual patients. Multidisciplinary Follow-up An ideal outpatient model consists of a multidisciplinary clinical team led by a neurologist with experience in autoimmune neurologic disorders. As the team leader, these neurologists can leverage the expertise of other members to address diagnostic uncertainty while providing anticipatory guidance and a detailed care plan. It is also paramount to look beyond the borders of neurology and to integrate other medical disciplines in the disease management (figure 2), similar to the approach taken for patients with other complicated neurologic disorders (e.g., amyotrophic lateral sclerosis). In this context, coordinated clinics have been shown to improve patients' care and quality of life while shifting care away from hospital-based health services, resulting in a potential cost savings to patients and health care systems.24 Figure 2 Autoimmune Neurology Interdisciplinary Care Model ADLs = activities of daily living; GI = gastroenterology; OT = occupational therapy; PM&R = physical medicine and rehabilitation; PT = physical therapy. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2021. All Rights Reserved. We should note that all the specialists do not need to reside within the same space, although a coordinated clinic can have obvious benefits for clinicians and providers alike. The linchpin to deliver multidisciplinary care is strong communication. This approach may require ongoing reassessment of interdepartmental workflows related to care delivery including coordinating appointment for patients. In addition, although team members may vary from center to center, the core principle remains the same: provide expert, holistic assessment, and treatment. Neurologist With Experience in Treating Autoimmune Disorders These specialists have specific training and knowledge that can promote early disease recognition. They also have detailed knowledge of and access to the newest generation of targeted IV monoclonal therapies while mitigating potential long-term complications from these therapies such as osteoporosis, infections, and progressive multifocal leukoencephalopathy. These specialists can also offer expertise in seronegative autoimmune neurologic cases, which are particularly challenging. For example, a short immunotherapy trial may be pursued when seronegative AE is suspected. There is limited evidence around these trials, and we would caution clinicians to have objective measures to determine the true efficacy of treatment. These measures may be framed around the most prominent or troublesome objective symptom, optimizing the ability to assess response to therapy and avoiding the need to rely on subjective perception of response, which is particularly susceptible to bias. For example, clinicians can use the Scale for the Assessment and Rating of Ataxia,25 the Symbol Digit Modalities Test, or the Montreal Cognitive Assessment 26 for reliable scores to measure the success of a trial. In addition to understanding the role of empiric immunotherapy trials, neurologists should have the experience and confidence to consider discontinuation of these trials based on objective findings or lack thereof. Neurologic Subspecialities Immune-mediated disorders may cause wide-ranging neurologic manifestations, necessitating broad consultation across neurologic and non-neurologic subspecialties. This can include cognitive and behavioral neurology (e.g., dementia), movement disorders (e.g., chorea, myoclonus, and cerebellar syndrome), epilepsy (e.g., autoimmune-related seizures), neuro-oncology (e.g., paraneoplastic disorders), sleep medicine (e.g., sleep apnea, narcolepsy, and disorders of arousal), and neuromuscular disorders (e.g., hyperexcitability disorders). An epileptologist with experience in treating AE is a particularly important partner. Immune-mediated epileptogenesis is a distinct entity recognized by the International League Against Epilepsy. Seizures are a common finding in AE and can be the manifestation of neurologic dysfunction that prompts patients to initially seek care. Even in the absence of overt seizures, repeated assessment for seizures including EEG monitoring is usually warranted.27 Clinical features that would support an immune-mediated basis include acute/subacute onset of focal seizures with an unusually high seizure frequency and a lack of response to standard AEDs.28 Once an autoimmune disorder is properly treated, AEDs may be tapered under the supervision and follow-up of an epileptologist.29,30 Neuropsychology Neuropsychologists play an important role in long-term follow-up, given the frequency and severity of cognitive impairment in recovering patients. Cognitive impairment can negatively affect employment, social engagement, and treatment adherence.31 Given these effects, appropriate identification and treatment of the specific domains affected in a patient endorsing cognitive dysfunction is especially warranted. Neuropsychologists can also help elucidate underlying tangentially related or confounding mood and/or behavioral symptoms. Psychiatry The recent focus on AE has further blurred the artificial distinction between neurology and psychiatry because most patients develop neuropsychiatric symptoms. In the end, collaboration between both disciplines is critical. Refractory psychosis may require the use of high-potency antipsychotic agents, which are associated with increased risks of extrapyramidal side effects, seizures' threshold, autonomic symptoms, neuroleptic malignant syndrome (especially in NMDAR encephalitis), and sedation.32,33 In addition, the medication used to treat AE can have a significant burden of psychiatric side effects (e.g., corticosteroids causing agitation and AEDs leading sedation). Many patients have persistent neuropsychiatric symptoms years out from their initial diagnosis.34 In NMDAR encephalitis, many patients will be on long-term psychotropic medication while also experiencing emotional lability and impulse control problems.35 Psychiatrists, especially those with experience in treating AE, are vital members of the treatment team. Collaboration between neurologists and mental health clinicians during hospitalization, at discharge, and throughout outpatient treatment is fundamental and can have a far-reaching effect on outcomes in AE cohorts.8 Rehabilitation Services Rehabilitation services are an integral part of the treatment and can focus on both physical and emotional well-being. This team encompasses physical medicine and rehabilitation specialists, psychologists, physical therapists, occupational therapists, social workers, and speech therapists. These services focus on a broad range of functions that can include ability to perform activities of daily living, mobility, return to work, and driving. The specific rehabilitation plan including whether the inpatient or outpatient setting is most appropriate is jointly developed between members of the treatment team. A medical social worker can also provide psychosocial support and evaluate for financial needs. They can connect patients/caregivers to advocacy groups, which can play a critical role in the recovery process and patient empowerment. Primary Care Clinicians Primary care clinicians play an essential role in providing support with ongoing health maintenance and managing comorbidities. This can also include counseling on healthy lifestyle measures that may promote recovery (e.g., smoking cessation, regular exercise, and diet) while ensuring that age-appropriate screening measures are completed. Furthermore, they can ensure that a patient's vaccination schedule is up to date because most of the immunotherapy used in the treatment of AE alter the immune response, which may be associated with an increased risk of infections and an impaired ability to mount an immune response. Proactive management through a partnership of patients, caregivers, and primary care clinicians is vital for long-term AE care. Long-term Prognosis A growing body of literature demonstrates the long-term cognitive, psychiatric, and physical sequelae experienced by patients with AE. In particular, nonmotor outcomes can be overlooked in routine practice but are of increasing importance to recovering patients and caregivers. In particular, cognitive impairment and psychiatric/behavioral sequelae complicate recovery and contribute to morbidity.8,36 Evidence citing “good outcomes” in AE is commonly defined as an mRS score of ≤2, which offers a very broad range in recovery as the scale is heavily weighted toward motor function. This measure neglects more meaningful outcomes such as resumption of gainful employment or schooling and establishment of personal relationships.6 It is imperative to consider these professional and social consequences because AE usually strikes young adults. Impairments relating to social behaviors can be slow to recovery and may limit functional independence. A group of nearly 60 patients with NMDAR encephalitis surveyed years out from their index diagnosis still identified factors foreshadowing a poor, long-term prognosis. Nearly one-third did not resume their prior work or schooling after their illness, whereas 20% of patients required special accommodations because of persistent deficits.8,37 Behavioral outcomes in broader cohorts (including antibody-negative AE patients) have shown similar results. In 1 study, only 50% of the patients had returned to work despite the fact that 85% were employed before the onset of symptoms. Most patients still required help with advanced activities of daily living including medication management, transportation, or managing household finances. When analyzing adaptive behaviors, patients scored lower on all measured domains. Of interest, patients with NMDAR encephalitis appeared to have better outcomes than did those with other forms of AE. This may be related to the increased clinical awareness of this disorder and offer hope that prompt recognition of other AE disorders can offer long-term improvement in functional domains.35 Other potential explanations may include the fact that patients with NMDAR encephalitis are typically younger with a greater potential for recovery,37 although there is evidence that patients on either age extreme (i.e., young children and older adults) tend to have worse clinical outcomes.4 Detailed neuropsychological profiles have confirmed executive dysfunction along with impairment in attention and working/episodic memory in some individuals' years after the NMDAR encephalitis index admission. These deficits are concordant with advanced imaging analyses. Resting-state functional MRI and diffusion tensor imaging have revealed reduced hippocampal functional connectivity and atrophy in patients with NMDAR encephalitis38 and LGI-1 antibody encephalitis.34 Safe return to driving is integral to a patient's independence, autonomy, and work/school enrollment. A study conducted at Washington University in St. Louis, Missouri, showed dynamic changes in the driving patterns of 5 recovering patients with NMDAR or LGI-1 antibody-mediated encephalitis. These patients took frequent, shorter trips earlier in their recovery, which may reflect a type of “self-regulation.” With time, these patients had normalization in their driving patterns, although there was a higher proportion of aggressive driving actions in the AE cohort when compared with controls.39 This group did not investigate whether there was any visual spatial dysfunction such as having trouble navigating new routes or forgetting where they parked their car. In another longitudinal LGI-1 study, 11 patients with reportedly good outcomes (i.e., mRS 0–2) showed inferior spatial recognition scores. This type of dysfunction can have pronounced impact on daily function and can be difficult to capture on our current outcome measures.13 Incorporating Research Into Multidisciplinary Care International, multicenter randomized controlled trials are needed to guide treatment in AE and limit variability in treatment approaches.40 A number of off-label immunotherapies have been proposed for AE, but there is no consensus on the type, timing, dose, or route of delivery of these agents.41 High-quality evidence is needed to inform the selection of safe and efficacious therapies. One of the strengths of a dedicated neurology clinic for autoimmune patients is the ability to offer unique opportunities for patients through clinical trial participation. These multidisciplinary autoimmune neurology clinics would be ideally positioned to serve as a portal to these studies. Research can span many relevant areas such as drug development, neuroimaging, genomics, quality of life, and behavioral studies including evaluation of neurocognitive outcomes. Furthermore, a biospecimen repository may be effectively used in these clinics to facilitate future research projects. Conclusion Autoimmune neurology is a rapidly developing subspecialty. Familiarity and awareness of different antibody-associated phenotypes can help to ensure prompt diagnosis and treatment. In cases that are less clear, a sound diagnostic approach anchored on objective clinical findings is important for optimizing outcomes. Clinical monitoring and treatment must expand beyond the acute care setting. A growing body of literature illustrates prolonged periods of recovery complicated by behavioral dysfunction and neuropsychiatric symptoms in the months to years after the diagnosis. These findings highlight the importance of comprehensive teams with expertise in autoimmune neurologic disorders. The ultimate goal is to provide optimal, long-term outpatient care coordinated among clinicians while anticipating the needs of the patients and caregivers. Study Funding The authors report no targeted funding. Disclosure J.R. Abbatemarco and S.J. Rodenbeck declare no disclosures relevant to the manuscript. G.S. Day: supported by a career development grant from the NIH (K23AG064029); he owns stock in ANI Pharmaceuticals (a generic pharmaceutical company); he serves as a topic editor for DynaMed (EBSCO), overseeing the development of evidence-based educational content, a consultant for Parabon Nanolabs (Inc.), and as the Clinical Director of the Anti-NMDA Receptor Encephalitis Foundation (Inc., Canada uncompensated). M.J. Titulaer: received funding from the Netherlands Organization for Scientific Research (NWO, Veni incentive), ZonMw (Memorabel program), and the Dutch Epilepsy Foundation (NEF 14-19 and 19-08); has filed a patent, on behalf of the Erasmus MC, for methods for typing neurologic disorders and cancer, and devices for use therein; has received research funds for serving on a scientific advisory board of MedImmune LLC, for consultation at Guidepoint Global LLC, for consultation at UCB, and for teaching colleagues by Novartis; and has received an unrestricted research grant from Euroimmun AG and from CSL Behring. A.K. Yeshokumar: currently an employee of Bristol Myers Squibb (but was not at the time that this work was completed). S.L. Clardy: editor, Neurology®Podcast and Neurology Minute; research and/or clinical fellowship support from the Western Institute for Veterans Research (WIVR), the Siegel Rare Neuroimmune Association (SRNA), the Sumaira Foundation for NMO, Alexion, Viela Bio, and the Barbara Gural Steinmetz Foundation; and consulting/ad board: Alexion, Genentech, Viela Bio, Guidepoint, and ExpertConnect (majority of fees paid to the University of Utah Development account). Go to Neurology.org/NN for full disclosures. Appendix Authors Footnotes Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article. The Article Processing Charge was funded by the authors. Received April 2, 2021. Accepted in final form May 3, 2021. Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. 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Arch Clin Neuropsychol. 2018;33(8):964-983.OpenUrl 32.↵Warren N, Siskind D, O'Gorman C. Refining the psychiatric syndrome of anti-N-methyl-d-aspartate receptor encephalitis. Acta Psychiatr Scand. 2018;138(5):401-408.OpenUrl 33.↵Lejuste F, Thomas L, Picard G, et al. Neuroleptic intolerance in patients with anti-NMDAR encephalitis. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e280. 34.↵Finke C, Pruss H, Heine J, et al. Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol. 2017;74(1):50-59.OpenUrl 35.↵Yeshokumar AK, Gordon-Lipkin E, Arenivas A, et al. Neurobehavioral outcomes in autoimmune encephalitis. J Neuroimmunol. 2017;312:8-14.OpenUrl 36.↵Yeshokumar AK, Blum RA, Randell T, Jette N, Easton A. Exploration of patient- and relative-reported outcomes of cognitive, emotional, and social function after encephalitis. Brain Inj. 2021;35(2):255-23.OpenUrl 37.↵de Bruijn M, Aarsen FK, van Oosterhout MP, et al. Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis. Neurology. 2018;90(22):e1997-e2005.OpenUrl 38.↵Finke C, Kopp UA, Scheel M, et al. Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2013;74(2):284-296.OpenUrlCrossRefPubMed 39.↵Day GS, Babulal GM, Rajasekar G, Stout S, Roe CM. The road to recovery: a pilot study of driving behaviors following antibody-mediated encephalitis. Front Neurol. 2020;11:678.OpenUrl 40.↵Dubey D, Britton J, McKeon A, et al. Randomized placebo-controlled trial of intravenous immunoglobulin in autoimmune LGI1/CASPR2 epilepsy. Ann Neurol. 2020;87(2):313-323.OpenUrlCrossRefPubMed 41.↵Ganesh A, Bartolini L, Wesley SF. Worldwide survey of neurologists on approach to autoimmune encephalitis. Neurol Clin Pract. 2020;10(2):140-148. 42.Di Lorenzo R, Mente K, Li J, et al. Low specificity of voltage-gated calcium channel antibodies in Lambert-Eaton myasthenic syndrome: a call for caution. J Neurol. 2018;265(9):2114-2119.OpenUrl 43.Zalewski NL, Lennon VA, Lachance DH, Klein CJ, Pittock SJ, McKeon A. P/Q- and N-type calcium-channel antibodies: oncological, neurological, and serological accompaniments. Muscle Nerve. 2016;54(2):220-227.OpenUrlPubMed 44.McKeon A, Lennon VA, Lachance DH, Fealey RD, Pittock SJ. Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments. Arch Neurol. 2009;66(6):735-741.OpenUrlCrossRefPubMed 45.Li Y, Jammoul A, Mente K, et al. Clinical experience of seropositive ganglionic acetylcholine receptor antibody in a tertiary neurology referral center. Muscle Nerve. 2015;52(3):386-391.OpenUrlPubMed 46.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.OpenUrlCrossRefPubMed 47.Gadoth A, Pittock SJ, Dubey D, et al. Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol. 2017;82(1):79-92.OpenUrlCrossRefPubMed 48.Valencia-Sanchez C, Pittock SJ, Mead-Harvey C, et al. Brain dysfunction and thyroid antibodies: autoimmune diagnosis and misdiagnosis. Brain Commun. 2021;3(2):fcaa233.OpenUrl 49.Mattozzi S, Sabater L, Escudero D, et al. Hashimoto encephalopathy in the 21st century. Neurology. 2020;94(2):e217-e224.OpenUrl 50.Pittock SJ, Yoshikawa H, Ahlskog JE, et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc. 2006;81(9):1207-1214.OpenUrlCrossRefPubMed 51.McKeon A, Tracy JA. GAD65 neurological autoimmunity. Muscle Nerve. 2017;56(1):15-27.OpenUrlPubMed 52.Budhram A, Sechi E, Flanagan EP, et al. Clinical spectrum of high-titre GAD65 antibodies. J Neurol Neurosurg Psychiatry. 2021 Feb 9:jnnp-2020-325275. doi:10.1136/jnnp-2020-325275. 53.Munoz-Lopetegi A, de Bruijn M, Boukhrissi S, et al. Neurologic syndromes related to anti-GAD65: clinical and serologic response to treatment. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e696. 54.Hesselmark E, Bejerot S. Biomarkers for diagnosis of pediatric acute neuropsychiatric syndrome (PANS): sensitivity and specificity of the Cunningham panel. J Neuroimmunol. 2017;312:31-37.OpenUrl
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Josep Dalmau receives the “Scientific Breakthrough 2023” Award from the American Brain Foundation

From www.clinicbarcelona.org - May 23, 2023 2:38 PM
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

From www.clinicbarcelona.org - September 5, 2023 11:21 AM
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

From youtu.be - August 6, 2023 7:10 PM
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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
From www.ajnr.org - July 27, 2023 11:18 AM
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
From jneuroinflammation.biomedcentral.com - July 27, 2023 11:01 AM
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
From jmedicalcasereports.biomedcentral.com - July 14, 2023 2:17 PM
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
From www.antinmdafoundation.org - June 25, 2023 2:58 PM
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
From nn.neurology.org - June 19, 2023 9:45 PM
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
From www.encephalitis.info - June 19, 2023 9:38 PM
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
From www.psychiatrist.com - June 19, 2023 9:33 PM
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
From jmedicalcasereports.biomedcentral.com - June 19, 2023 9:27 PM
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
From cp.neurology.org - June 14, 2023 7:42 PM
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
From pubmed.ncbi.nlm.nih.gov - June 14, 2023 7:41 PM
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
From www.frontiersin.org - September 5, 2023 11:22 AM
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

Enceph-IG Study - Institute of Infection, Veterinary and Ecological Sciences - University of Liverpool | AntiNMDA | Scoop.it
From www.liverpool.ac.uk - August 6, 2023 7:27 PM
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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
From touchneurology.com - July 27, 2023 11:22 AM
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
From news.mayocliniclabs.com - July 27, 2023 11:05 AM
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New center to spotlight neurological autoimmune disorders

New center to spotlight neurological autoimmune disorders | AntiNMDA | Scoop.it
From bioengineer.org - July 14, 2023 2:19 PM
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
From news.mayocliniclabs.com - July 14, 2023 2:16 PM
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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
From blogs.cardiff.ac.uk - June 19, 2023 9:46 PM
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30 neurological disorders every doctor should know about –

30 neurological disorders every doctor should know about – | AntiNMDA | Scoop.it
From theneurologylounge.com - June 19, 2023 9:42 PM
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
From pubmed.ncbi.nlm.nih.gov - June 19, 2023 9:34 PM
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
From www.cbc.ca - June 19, 2023 9:28 PM
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
From myhealthcrm.com - June 14, 2023 7:43 PM
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
From pubmed.ncbi.nlm.nih.gov - June 14, 2023 7:41 PM
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
From www.wndu.com - June 14, 2023 7:40 PM
(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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