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Neuropsychiatry: Where Are We And Where Do We Go From Here?

Neuropsychiatry: Where Are We And Where Do We Go From Here? | AntiNMDA | Scoop.it
Neuropsychiatry has generally been regarded as a hybrid discipline that lies in the borderland between the disciplines of psychiatry and neurology. There is much debate on its current and future identity and status as a discipline.Taking a historical ...
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New Prize offered by The Anti-NMDA Receptor Encephalitis Foundation at the 54th annual Congress of the Canadian Neurological Sciences Federation

New Prize offered by The Anti-NMDA Receptor Encephalitis Foundation at the 54th annual Congress of the Canadian Neurological Sciences Federation | AntiNMDA | Scoop.it
The Foundation is delighted and honoured to sponsor a prize at the annual meeting of the Canadian Neurological Sciences Federation in Montreal, Québèc on 16 ...Read More...
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Anti-NMDA-receptor encephalitis: A neuropsychiatric syndrome associated with ovarian teratoma

Anti-NMDA-receptor encephalitis: A neuropsychiatric syndrome associated with ovarian teratoma | AntiNMDA | Scoop.it
3. Comment Anti-NMDA-receptor encephalitis was initially described in 1997, in two separate reports of young women. These women presented with an ovarian teratoma and symptoms that included psychiatric manifestations and altered level of consciousness. In both patients, there was a gradual significant improvement in symptoms after tumor removal (Nokura et al., 1997, Okamura et al., 1997). In 2005, a series of four women with ovarian teratoma, psychiatric symptoms, altered level of consciousness and central hypoventilation was described. Authors hypothesized that the syndrome was a paraneoplastic process due to an antibody to an unknown antigen expressed in the hippocampus (Vitaliani et al., 2005). The associated antibody was discovered to be anti-NMDA-receptor in 2007 (Dalmau and Tüzün, 2007). In subsequent years, hundreds of cases have been reported in the neurology literature in both men and women, with approximately 80% of cases in females (Mann et al., 2014). The median age at onset of symptoms is 21 years old, although cases have been reported in patients ranging from 8 months to 85 years (Titulaer et al., 2013, Dalmau et al., 2011). Teratomas are found in large numbers of patients, most commonly in women between age 12 and 45 and in patients of Asian or African American descent (Titulaer et al., 2013, Dalmau et al., 2011). Most commonly, these are ovarian teratomas, though other germ-cell and rarely non-germ cell tumors have also been described in association with anti-NMDA-receptor encephalitis (Dalmau and Tüzün, 2007, Titulaer et al., 2013, Dalmau et al., 2011). Three cases have been described in pregnant women, all of whom recovered after removal of their ovarian teratoma and immunosuppression. Two of these women went on to have healthy infants, while one underwent termination of pregnancy (Kumar et al., 2010). The syndrome often begins with viral-like symptoms including headache, nausea, vomiting, fever, and fatigue (Dalmau et al., 2011). The non-specific nature of these symptoms generally precludes diagnosis at this stage and is recognized as a prodrome only after the illness progresses with a spectrum of neuropsychiatric symptoms. These symptoms have been divided into early and late stage symptoms. Early stage symptoms generally present with two weeks of prodromal symptoms and include confusion, memory loss, paranoia, hallucinations, mood disturbances, anxiety, self-harming behaviors, seizures and movement disorders such as facial twitching and choreoathetosis (Dalmau et al., 2011). As the psychiatric symptoms are often the most prominent, 77% of patients are initially seen by psychiatrists (Mann et al., 2014), and many patients are diagnosed with new-onset psychiatric disorders. However, these patients do not respond to anti-psychotics and progress to late stage symptoms, such as decreased responsiveness, hypoventilation, and autonomic instability including hypotension or hypertension, bradycardia or tachycardia, hyperthermia, and urinary incontinence (Mann et al., 2014). In patients with acute onset of psychiatric symptoms with any neurologic findings, or symptoms unresponsive to anti-psychotic medications, the diagnosis of encephalitis should be considered. In particular, serum and CSF studies for markers of viral and autoimmune causes of encephalitis, MRI, and electroencephalogram (EEG) may be useful in obtaining a diagnosis. Of note, while MRI may be normal in two-thirds of patients with anti-NMDA-receptor encephalitis, EEG abnormalities are seen in more than 90% of these patients (Titulaer et al., 2013). Definitive diagnosis is made when anti-NMDA-receptor antibodies are detected in the blood or CSF (Titulaer et al., 2013, Dalmau et al., 2011). Once definitive diagnosis has been obtained, imaging studies such as pelvic ultrasound, MRI, computed tomography, and positron emission tomography may be used to evaluate for an underlying teratoma. In rapidly-deteriorating patients in whom anti-NMDA-receptor encephalitis is highly suspected, but not yet confirmed, providers may consider imaging and removal of any detected neoplasms, as in this case. Delayed treatment may result in progression of the autoimmune process with associated clinical deterioration to autonomic instability, catatonia, status epilepticus, or coma. In one series of patients with anti-NMDA-receptor encephalitis, five out of six patients with an ovarian teratoma who did not undergo surgery died (Titulaer et al., 2013). In contrast, removal of the tumor may be curative. In approximately 80% of patients who undergo tumor removal and immunosuppressive treatment, substantial neurological improvement occurs (Dalmau et al., 2011). In the case above and in previously reported cases, symptoms of anti-NMDA-receptor encephalitis markedly improved within one month of tumor removal and immunosuppressive treatment, though recovery can continue for up to 24 months (Titulaer et al., 2013, Dalmau et al., 2011). Multiple regimens of immunosuppressive treatments have been described, including first line treatment with intravenous steroids and intravenous immunoglobulins (IVIG) or plasmapheresis and second line treatment with rituximab and cyclophosphamide (Titulaer et al., 2013, Dalmau et al., 2011). For the patient described above, a modified version of the BrainWorks protocol for severe antibody-mediated inflammatory brain disease was used (BrainWorks). This protocol consists of 1 g prednisone daily for three to seven days, followed by 60 mg daily for one month, followed by a six-month taper. Simultaneously, patients receive seven plasmapheresis treatments over 14 days, 70 g of IVIG every two weeks for five doses, rituximab 500 mg/m2 in two doses two weeks apart, and daily calcium and vitamin D supplementation. This protocol was developed by the BrainWorks Network based on experience from a web-based, international prospective cohort of pediatric patients with inflammatory brain diseases. It differs from previously described protocols (Titulaer et al., 2013, Dalmau et al., 2011) in that it is based solely on experience in the pediatric population, and includes rituximab in the initial treatment, rather than using it as a second line agent. In patients with no detectable underlying neoplasms, it has been hypothesized that the syndrome may be caused by microscopic germ cell tumors undetectable by imaging (Mann et al., 2014). This hypothesis is supported by the findings that recovery is more common and relapse less likely in patients with a detectable tumor (Dalmau et al., 2011). In addition, there have been reported cases of ovarian teratomas being detected years after presentation of anti-NMDA-receptor encephalitis symptoms (Mann et al., 2014). Therefore, for patients without detectable tumors, it is recommended to continue immunosuppression with azathioprine or mycophenolate for a minimum of 1 year after symptom relapse, and in female patients over age 12 without detectable tumors, to screen for ovarian teratomas with pelvic MRI or ultrasound every 6 months for 4 years (Mann et al., 2014, Titulaer et al., 2013, Dalmau et al., 2011). Following neurologic recovery, women of childbearing potential should receive counseling on contraception, particularly for those remaining on azathioprine and mycophenolate. These medications are both classified as Pregnancy Category D. These women should have a pregnancy test prior to treatment initiation and as indicated at follow up visits. For mycophenolate in particular, it is recommended to avoid pregnancy for an additional 6 weeks following discontinuation of treatment. Particular consideration should be given to use of long-acting reversible contraceptives in these patients given that many may have residual cognitive deficits including difficulties with memory and impulsivity that may make consistent contraceptive use more challenging. With appropriate diagnosis and rapid treatment, including resection of any underlying teratoma and immunosuppression, patients with anti-NMDA-receptor encephalitis have a high likelihood of a positive outcome. The gynecologist has an important role to play within the multidisciplinary team caring for these patients as early tumor detection and removal results in an improved prognosis, and those without tumors require frequent monitoring for tumor development.
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Optic neuritis as the initial clinical presentation of limbic encephalitis: a case report | Journal of Medical Case Reports | Full Text

Optic neuritis as the initial clinical presentation of limbic encephalitis: a case report | Journal of Medical Case Reports | Full Text | AntiNMDA | Scoop.it
Limbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors.
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Autoimmune Channelopathies of the Nervous System

Autoimmune Channelopathies of the Nervous System | AntiNMDA | Scoop.it
Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle.
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Buy PDF - Unusual case of anti-N-methyl-D-aspartic acid-receptor (NMDA-R) encephalitis and autoimmune polyglandular syndrome (APS)

Buy PDF - Unusual case of anti-N-methyl-D-aspartic acid-receptor (NMDA-R) encephalitis and autoimmune polyglandular syndrome (APS) | AntiNMDA | Scoop.it
Frunza-Stefan, S.; Whitlatch, H.B.; Rao, G.G.; Malek, R., 2018: Unusual case of anti-N-methyl-D-aspartic acid-receptor (NMDA-R) encephalitis and autoimmune polyglandular syndrome (APS)...
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Female-Dominant Autoimmunity: The Role of Progesterone –

Female-Dominant Autoimmunity: The Role of Progesterone – | AntiNMDA | Scoop.it
TOLLE CAUSAM Tanya Lee, ND We are just beginning to understand the complex nature of the immune system and the cross-talk between the immune system and other systems in the body. The influence of sex hormones is not limited to reproductive tissues; they also exert effects on peripheral systems such as the immune system. In the context of autoimmune disease, there is a known female predominance of many autoimmune diseases. Some examples of female-to-male ratios of specific autoimmune diseases include 16:1 for primary biliary cirrhosis; 12:1 for antiphospholipid syndrome; 9-10:1 for systemic lupus erythematosus (SLE); and 2:1 for multiple sclerosis.1,2 Other autoimmune conditions with female predominance include Hashimoto’s thyroiditis, Graves’ disease, scleroderma, and Sjögren’s syndrome.2 The female predominance of autoimmune disease is highlighted by the fact that the onset of most female-dominant autoimmune diseases occurs following puberty. The ratio of female-to-male risk of SLE and thyroiditis before puberty is lower (3-4:1) than after puberty (9:1), and other autoimmune diseases, such as Sjögren’s syndrome and primary biliary cirrhosis, are extremely rare in pediatric populations.2 Autoimmune diseases whose onset typically occurs before puberty, eg, type 1 diabetes mellitus, appear to exhibit no female polarization.2 The role of female hormones in autoimmune disease is also observed in symptom severity fluctuations throughout the different phases of the menstrual cycle.3 Both genetic and environmental factors contribute to the risk of autoimmune disease: when genetic risk is high, environmental factors become less influential on the onset and severity of disease progression. Although hormone status may play a role in the risk of developing disease, research has thus far found that modulating hormones appears to impact disease activity far more than disease risk.2 While sexual dimorphism of autoimmune disease includes many hormonal factors, female prevalence of certain autoimmune diseases suggest that sex hormones such as estrogen and progesterone are key players in the development and activity of the female-prevalent autoimmune diseases. Pregnancy is an excellent example for viewing how sex hormones may influence the immune system. There is a dramatic change in hormones during pregnancy, with progesterone and estrogen levels increasing 5-10-fold within the maternal circulation, and then dropping suddenly drop postpartum, alongside significant immunological shifts both during and after pregnancy.2 During pregnancy, the immune system must achieve a unique state of equilibrium: being strong and active at the maternal-fetal interface, while also maintaining a state of immunosuppression within the maternal circulation so as to not react to the partially allogenic cells of the fetus. During pregnancy, the uterine lining (the decidua) is an immunologically intense area, tightly regulated in order to ensure the survival of the fetus. Specialized uterine natural killer cells and monocytes are inactivated when encountering the unique HLA-G expression of fetal trophoblastic cells, but are active at disabling any foreign pathogen threatening the fetus.4 Other known mechanisms of this pregnancy paradox include T-helper-2 (Th2) dominance, upregulation of anti-inflammatory cytokines and immunosuppressive proteins, downregulation of the classical complement pathway, and the blockage of fetal antigen exposure to the maternal immune system.2,5 The local protective effects of the maternal-fetal interface appear to be influenced by estrogen and progesterone. While estrogen as well as other steroids play a large role in the totality of the immunological paradox of pregnancy and the development and progression of autoimmune disease, this article will focus on the effects of progesterone on the immune system during pregnancy and in female-prevalent autoimmune disease. PROGESTERONE’S BROAD ACTIONS PROGESTERONE & THE IMMUNE SYSTEM Progesterone is a steroid hormone produced by the corpus luteum, uterus, adrenal glands, and the brain. Progesterone (P4) binds to many different receptors on both reproductive and non-reproductive tissues; these receptors include membrane-bound progesterone receptors, intracellular progesterone receptors, and glucocorticoid receptors, which are expressed on human immune cells including mast cells, natural killer (NK) cells, macrophages, dendritic cells, and both CD4+ and CD8+ type cells.2,3 P4 is generally considered an anti-inflammatory hormone. Some of its known anti-inflammatory mechanisms include the suppression of proinflammatory Th1 and Th17 differentiation, T-regulatory (T-reg) cell induction and expansion (immune modulating), as well as polarization towards Th2 differentiation and activity.6 PROGESTERONE IN PREGNANCY Progesterone is secreted by the corpus luteum in the early stages of pregnancy, and later by the placenta after week 8 of gestation. P4 levels rise 10-fold within the maternal circulation and 100-fold within the placenta.3 This high concentration of P4 is strong enough to signal through the glucocorticoid receptor, which is thought to be one of the mechanisms for the immunosuppressive effect seen during pregnancy.7 The surge of P4 is credited for Th2 shift, for the expansion and production of the Th2-promoting cytokine, interleukin (IL)-4, the increased expression of uterine NK cells, the suppression of inflammatory cytokine, Th17, and the induction of the T-reg cells during pregnancy.2,3 A recent study by Shah et al observed that administration of progesterone to healthy, pregnant women suppressed the production of interferon-gamma (IFN-γ), a promoter of Th1-mediated immunity. The study also found that mifepristone, a progesterone receptor antagonist, induced IFN-γ expression.8 PROGESTERONE & AUTOIMMUNE DISEASE The transient modification of the immune system during pregnancy and the clear influence of pregnancy on the presentation of different autoimmune conditions serves as a gateway for our understanding of the role progesterone plays in autoimmune disease. While research specifically studying the effects of natural P4 is still lacking, a strong backbone of evidence suggests that therapeutic use of P4 in certain autoimmune diseases may be beneficial in modulating the activity of the disease. RHEUMATOID ARTHRITIS The hormonal influence in rheumatoid arthritis (RA) is illustrated by the symptomatic changes that occur with the fluctuations of the menstrual cycle, the remission of symptoms during pregnancy, and the increase in flares in the postpartum period.9,10 RA onset typically occurs after menopause (45-75 years) and nulliparity appears to increase the risk of developing RA, suggesting that estrogen and progesterone may play a protective role in the risk and disease activity of RA.11 The rapid withdrawal of progesterone postpartum may contribute to the increase in risk of RA in susceptible women after delivery.12 In RA, there is a marked increase in the inflammatory Th17; as discussed, progesterone has been found to induce T-reg cells, suppress Th17 and Th1 differentiation, and promote Th2 dominance, suggesting its protective role in RA. An earlier study by Valentino et al found that women with RA exhibited significantly lower progesterone levels during the luteal phase of the menstrual cycle as compared to healthy controls.13 However, there is very little in the way of evidence supporting the use of progesterone alone for managing the risk and activity of RA. In fact, many studies (both in vivo and human) fail to show consistent results regarding the influence of P4 in RA, with many showing no amelioration of symptoms of RA by hormone replacement therapy (HRT).11,14,15 MULTIPLE SCLEROSIS Multiple sclerosis (MS) is an autoimmune condition targeting the central nervous system, driven by myelin-specific CD4+ Th1 cells and inflammatory cytokines. Considering the Th2-promoting effect of progesterone, and its known neuroprotective, anti-inflammatory and pro-myelinating properties, this hormone has been a therapy of interest for modulating disease activity in MS.16 Similar to RA, the hormonal impact of progesterone on disease activity in MS is represented by the amelioration of symptoms during pregnancy and the increase in disease flares within the postpartum period.2 The immunomodulatory effect of progesterone can be observed in animal models of experimental autoimmune encephalitis (EAE) – the in-vivo representation of MS. These animal models have shown that, at the onset of EAE, progesterone can suppress inflammation by reducing proinflammatory IL-2, IL-17, and IL-23, and increasing B-cells and anti-inflammatory IL-10, thereby reducing the severity of disease progression.17 In another in-vivo model of demyelination, Ye et al found that treatment of progesterone at the onset of disease ameliorated demyelination and the resulting neurobehavioral deficits.18 An ongoing human clinical trial plans to determine the effects of high-dose progestin administration on postpartum MS flares at the onset of the postpartum period.19 SYSTEMIC LUPUS ERYTHEMATOSUS The typical onset of SLE, occurring between menarche and menopause, as well as the high female:male dominance (9:1) of this disease, suggest that hormones play a role in the development and activity of SLE.11 Early menarche is considered an independent risk factor for SLE, and initial SLE flares in women have been linked to low P4, indicating a pathogenic role of estrogen and a protective role of P4 in both the risk and activity of SLE.11 Symptoms of SLE have been found to be exacerbated by pregnancy, with SLE flare rates higher in pregnant patients compared to non-pregnant patients.20 SLE flares have been associated with Th2 dominance and increased humoral activity, a state that is favorable for other autoimmune conditions, such as RA and MS.3 However, there is also evidence that pregnancy itself does not influence the risk of SLE flares and that the biggest risk factor for SLE flares during pregnancy is the severity of disease activity 6 months prior to conception, as well as the discontinuation of medication at the onset of pregnancy.21 Therefore, high circulating levels of hormones may not actually influence disease activity in SLE, as compared with autoimmune conditions such as RA and MS. A link has been observed between estrogen-containing HRT and oral contraceptive (OCP) use, as well as a dose-dependent relationship between the level of estrogen in HRT/OCPs and the risk for SLE flares in those with active disease.22,23 SLE patients often experience P4 deficiency during the luteal phase of the menstrual cycle, suggesting that P4 may have a protective role against SLE; however, it is unknown if this is a consequence of the disease or a risk factor.2 Progestin-only forms of OCPs and HRT do not appear to increase risk and can even reduce flares of SLE.24 High circulating levels of type 1 IFN-α and IFN-ß are a hallmark of SLE.3 A recent study found that progestogens (natural progesterone and synthetic medroxyprogesterone acetate) appear to suppress plasmacytoid dendritic cell production of IFN-α, as well as the activation of the IFN-inducing transcription factor IRF-5.25 This indicates that modifying P4 levels may be an effective target for modulating disease risk and activity of SLE. While there is some evidence to suggest that there is no conferred difference in the risk of SLE flares between combined and progestin-only OCPs and copper IUDs, other studies suggest that estrogen is an aggravating factor in terms of a link between SLE flares and HRT.2 However, especially considering the high risk for thrombosis in SLE patients (specifically those with high anti-phospholipid antibodies), progesterone-only OCPs should be considered for SLE patients seeking oral forms of contraception.2 CLINICAL CONSIDERATIONS While many experimental animal models indicate that progesterone may have a large impact on immunological function and disease activity of autoimmune conditions, human clinical trials are greatly lacking. Existing observational studies on the impact of HRT and OCPs on autoimmune disease typically used synthetic progestins to represent P4 activity rather than bioidentical P4, which would typically be the treatment of choice by naturopathic doctors. Considering the influence of physiological P4 on immune function observed in pregnancy when P4 levels are peaked, it may be safe to assume that bioidentical P4 represents a viable treatment option to mimic these effects. Another consideration are the inconsistent results from using HRT in autoimmune disease. Many of these studies fail to provide treatments that mimic the physiological levels of pregnancy; the activity of progesterone on progesterone- and glucocorticoid receptors (GRs) is dose-dependent, with the latter requiring extremely high levels of P4 (pregnancy levels) for activation.2 GR activation has been proposed as the main mechanism of immune modulation by P4, given that these receptors are highly expressed on immune cells and that steroids that bind to the GRs (ie, corticosteroids) are the standard treatment for inflammatory flares in autoimmune disease.26 Perhaps dosing bioidentical progesterone at levels mimicking pregnancy can produce more consistently positive results. Considering the currently available research, bioidentical progesterone may be a viable option in modifying disease activity in female-dominant autoimmune diseases. Clinicians should base this treatment on the patient’s individual requirements – the category of autoimmune disease (ie, whether it is a female-dominant type) and outcomes of progesterone testing. A detailed history of menstrual cycle activity and fertility should be used to help determine whether progesterone might be a treatment of value for an autoimmune patient. Autoimmune diseases still remain as complex, multifactorial conditions that are influenced by genetic, stochastic, and environmental triggers. It would be silly to consider hormones to be a sole contributing factor when managing female-dominant autoimmune disease. However, insights into how hormones impact risk and disease activity in autoimmune disease provide clinicians a valuable tool to consider when treating autoimmune patients. References: Borchers AT, Naguwa SM, Keen CL, Gershwin ME. The implications of autoimmunity and pregnancy. J Autoimmun. 2010;34(3):J287-J299. Hughes GC. Progesterone and autoimmune disease. Autoimmun Rev. 2012;11(6-7):A502-A514. Tan IJ, Peeva E, Zandman-Goddard G. Hormonal modulation of the immune system – A spotlight on the role of progestogens. Autoimmun Rev. 2015;14(6):536-542. Pazmany L, Mandelboim O, Vales-Gomez M, et al. Protection from natural killer cell-mediated lysis by HLA-G expression on target cells. Science. 1996;274(5288):792-795. Poole JA, Claman HN. Immunology of pregnancy. Implications for the mother. Clin Rev Allergy Immunol. 2004;26(3):161-170. Hughes GC, Clark EA, Wong AH. The intracellular progesterone receptor regulates CD4+ T cells and T cell-dependent antibody responses. J Leukoc Biol. 2013;93(3):369-375. Ugor E, Prenek L, Pap R, et al. Glucocorticoid hormone treatment enhances the cytokine production of regulatory T cells by upregulation of Foxp3 expression. Immunobiology. 2018;223(4-5):422-431. Shah NM, Imami N, Johnson MR. Progesterone Modulation of Pregnancy-Related Immune Responses. Front Immunol. 2018;9:1293. Latman NS. Relation of menstrual cycle phase to symptoms of rheumatoid arthritis. Am J Med. 1983;74(6):957-960. de Man YA, Dolhain RJ, Hazes JM. Disease activity or remission of rheumatoid arthritis before, during and following pregnancy. Curr Opin Rheumatol. 2014;26(3):329-333. Hughes GC, Choubey D. Modulation of autoimmune rheumatic diseases by oestrogen and progesterone. Nat Rev Rheumatol. 2014;10(12):740-751. Alpizar-Rodriguez D, Pluchino N, Canny G, et al. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology (Oxford). 2017;56(8):1254-1263. Valentino R, Savastano S, Tommaselli AP, et al. Hormonal pattern in women affected by rheumatoid arthritis. J Endocrinol Invest. 1993;16(8):619-624. Ganesan K, Balachandran C, Manohar BM, Puvanakrishnan R. Comparative studies on the interplay of testosterone, estrogen and progesterone in collagen induced arthritis in rats. Bone. 2008;43(4):758-765. Holroyd CR, Edwards CJ. The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus. Climacteric. 2009;12(5):378-386. De Nicola AF, Gonzalez Deniselle MC, Garay L, et al. Progesterone protective effects in neurodegeneration and neuroinflammation. J Neuroendocrinol. 2013;25(11):1095-1103. Yates MA, Li Y, Chlebeck P, et al. Progesterone treatment reduces disease severity and increases IL-10 in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2010;220(1-2):136-139. Ye JN, Chen XS, Su L, et al. Progesterone alleviates neural behavioral deficits and demyelination with reduced degeneration of oligodendroglial cells in cuprizone-induced mice. PLoS One. 2013;8(1):e54590. Vukusic S, Ionescu I, El-Etr M, et al. The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPART’MUS) trial: rationale, objectives and state of advancement. J Neurol Sci. 2009;286(1-2):114-118. Ruiz-Irastorza G, Lima F, Alves J, et al. Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies. Br J Rheumatol. 1996;35(2):133-138. Barbhaiya M, Bermas BL. Evaluation and management of systemic lupus erythematosus and rheumatoid arthritis during pregnancy. Clin Immunol. 2013;149(2):225-235. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. 2007;56(4):1251-1262. Bernier MO, Mikaeloff Y, Hudson M, Suissa S. Combined oral contraceptive use and the risk of systemic lupus erythematosus. Arthritis Rheum. 2009;61(4):476-481. Chabbert-Buffet N, Amoura Z, Scarabin PY, et al. Pregnane progestin contraception in systemic lupus erythematosus: a longitudinal study of 187 patients. Contraception. 2011;83(3):229-237. Hughes GC, Thomas S, Li C, et al. Cutting edge: progesterone regulates IFN-alpha production by plasmacytoid dendritic cells. J Immunol. 2008;180(4):2029-2033. Flammer JR, Rogatsky I. Minireview: Glucocorticoids in autoimmunity: unexpected targets and mechanisms. Mol Endocrinol. 2011;25(7):1075-1086. Tanya Lee, ND, received her Bachelor of Science degree (Honours) in Biochemistry and Biomedical Sciences from McMaster University, and was trained as a naturopathic doctor at the Canadian College of Naturopathic Medicine. Dr Lee practices full-time between 2 clinics, located in Toronto and Milton, Ontario. Although her primary-care practice focuses on family medicine, Dr Lee treats a wide variety of conditions, including endocrine disorders, infertility, digestive problems, cardiovascular disease, diabetes, insomnia, and fatigue. She has a special interest in the treatment of autoimmune diseases, as well as pediatric health.
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Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and... - PubMed - NCBI

Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and... - PubMed - NCBI | AntiNMDA | Scoop.it
Lancet Neurol. 2018 Sep;17(9):760-772. doi: 10.1016/S1474-4422(18)30244-8. Epub 2018 Jul 23.
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Limbic Encephalitis | International Psychogeriatric Association

Limbic Encephalitis | International Psychogeriatric Association | AntiNMDA | Scoop.it
Dr. Laura Valzolgher reviews the diagnostic criteria for Limbic Encephalitis along with treatment and outcomes.
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Acta Neurologica Belgica, Volume 118, Issue 4 - Springer

Acta Neurologica Belgica, Volume 118, Issue 4 - Springer | AntiNMDA | Scoop.it
Browse Volumes & Issues Volume 118, Issue 4, December 2018 ISSN: 0300-9009 (Print) 2240-2993 (Online) In this issue (21 articles) Previous Page of 2 Abstracts Clinical Practice Update 2018 Symposium of the Belgian Neurological Society 09th of June 2018 Pages 529-532 Letter to the Editor Herpes simplex encephalitis relapse associated with positive N-methyl-d-aspartate receptor antibodies Sabina Boangher, Pascal Mespouille, Sophie Goffette… Pages 533-535 Letter to the Editor Short-term outcome of carotid dissecting pseudoaneurysm: is it always benign? Loris Poli, Dikran Mardighian, Massimo Gamba… Pages 537-539 Letter to the Editor A case of adult-onset poststreptococcal opsoclonus–myoclonus syndrome Borislav Radic, Ivana Cajic, Zeljka Petelin Gadze… Pages 541-542 Letter to the Editor Paraplegia following lumbar puncture: a rare complication in spinal dural arteriovenous fistula Arman Çakar, Halil İbrahim Akçay, Tuncay Gündüz, Murat Kürtüncü Pages 543-545 Letter to the Editor Jaw clonus and opercular syndrome in ALS: a rare and interesting finding Alvee Saluja, Rajesh Kumar Singh, Deepa Dash, Rohit Bhatia… Pages 547-548 Letter to the Editor Vertebral artery dissection and golf swing: a paradigmatic new case Carlo Civardi, Alessandra Collini, Egidio Genovese… Pages 549-552 Letter to the Editor Influenza-associated encephalopathy with extensive reversible restricted diffusion within the white matter N. Kirat, H. De Cauwer, B. Ceulemans, D. Vanneste, A. Rossi Pages 553-555 Neuro-Images Innominate artery dissection and stroke after rifle recoil Isabelle Francillard, Lou Grangeon, Aude Triquenot-Bagan… Pages 557-559 Original Article Percutaneous balloon compression for persistent or recurrent trigeminal neuralgia after microvascular decompression: personal experience of 28 patients Wu Xu, Chengrong Jiang, Chen Yu, Weibang Liang Pages 561-566 Original Article Becker’s myotonia: novel mutations and clinical variability in patients born to consanguineous parents Ibrahim Sahin, Haktan B. Erdem, Huseyin Tan, Abdulgani Tatar Pages 567-572 Original Article High angular resolution diffusion imaging correlates of depression in Parkinson’s disease: a connectometry study Farzaneh Ghazi Sherbaf, Kaveh Same, Mohammad Hadi Aarabi Pages 573-579 Original Article Horizontal gaze deviation on computed tomography: the visual criterion and lesion characteristics in ischemic stroke Makoto Kobayashi Pages 581-587 Original Article Factors associated with deterioration of health-related quality of life in multiple system atrophy: 1-year follow-up study Milica V. Jecmenica-Lukic, Tatjana D. Pekmezovic… Pages 589-595 Original Article Anatomical relationship between carotid artery and styloid and hyoid bones in patients showing unintended head rotation on CTA Dimitri Renard, Lavinia Tatu Pages 597-602 Original Article Probable pathogenesis, diagnosis, and management of untreated arteriovenous malformation with cyst formation: case report and literature review Yu-Tse Liu, Tao-Chieh Yang, Shih-Ming Jung, Cheng-Chi Lee Pages 603-605 Original Article Early-onset dementia, leukoencephalopathy and brain calcifications: a clinical, imaging and pathological comparison of ALSP and PLOSL/Nasu Hakola disease C. Coomans, A. Sieben, M. Lammens, C. Ceuterick-de Groote… Pages 607-615 Original Article IgG4-related inflammatory pseudotumor of the brain parenchyma: a case report and literature review Zhuqing Zhang, Weiwei Fu, Minghui Wang, Lei Niu, Bin Liu… Pages 617-627 Original Article ALS and CHARGE syndrome: a clinical and genetic study Carmine Ungaro, Luigi Citrigno, Francesca Trojsi… Pages 629-635 Download PDF (1095KB) View Article Original Article The MMSE should not be the sole indicator of fitness to drive in mild Alzheimer’s dementia D. Piersma, A. B. M. Fuermaier, D. de Waard, P. P. De Deyn… Pages 637-642 Download PDF (723KB) View Article Previous Page of 2
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The Anti-NMDA Receptor Encephalitis Foundation Newsletter

The Anti-NMDA Receptor Encephalitis Foundation Newsletter | AntiNMDA | Scoop.it
New Prize offered by The Anti-NMDA Receptor Encephalitis Foundation at the 54th annual Congress of the Canadian Neurological Sciences Federation...
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Proportion and spectrum of movement disorders in adolescent and adult patients of autoimmune encephalitis of non-neoplastic aetiology. - PubMed - NCBI

Proportion and spectrum of movement disorders in adolescent and adult patients of autoimmune encephalitis of non-neoplastic aetiology. - PubMed - NCBI | AntiNMDA | Scoop.it
J Clin Neurosci. 2018 Nov 16. pii: S0967-5868(18)30917-2. doi: 10.1016/j.jocn.2018.10.076.[Epub ahead of print]...
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The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders - Damato - 2018 - Movement Disorders - Wiley Online Library

ABSTRACT An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody‐mediated movement disorders, and outline increasingly well‐established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation. Despite these advances, and the increasingly robust evidence for improved clinical outcomes with early escalation of immunotherapies, the underlying cellular immunology of these conditions has received little attention. Therefore, here, we outline the likely roles of T cells and B cells in the generation of autoantibodies, and reflect on how these may guide both current immunotherapy regimes and our future understanding of precision medicine in the field. In addition, we summarise potential mechanisms by which these peripherally‐driven immune responses may reach the central nervous system. We integrate this with the immunologically‐relevant clinical observations of preceding infections, tumours and human leucocyte antigen‐associations to provide an overview of the therapeutically‐relevant underlying adaptive immunology in the autoantibody‐mediated movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. The spectrum of autoantibody‐mediated movement disorders includes a broad and clinically heterogeneous group of conditions. The movement disorders occur either in isolation or, more commonly, as prominent and often distinctive manifestations of autoimmune encephalitides. Patients typically present with a subacute onset and multifocal neurological features involving the cortex, basal ganglia, brain stem, and/or spinal cord (Table 1). Although formal epidemiological data are still emerging, it is clear that both sexes and patients of all ages can be affected by this spectrum of disorders. The detection of neuronal autoantibodies in serum and the CSF can help to guide the diagnostic process, prognosis, and the treatment of these disorders. In addition, the autoantibody specificity may predict an underlying tumour association (Table 1). Perhaps most important, many of these conditions respond to immunotherapies, making them one of the earliest therapeutic considerations in the correct clinical context.1-5 Antigen Movement disorders Additional features Tumour association Extracellular antigens NMDA receptor Orobuccolingual dyskinesia, catatonia, limb dystonia, stereotypies, chorea Amnesia, psychiatric features, seizures, dysautonomia, coma Ovarian teratoma (especially if > 18 years old) LGI1 Faciobrachial dystonic seizures, myoclonus, chorea, parkinsonism LE, hyponatremia Thymoma, SCLC CASPR2 Chorea, ataxia LE, Morvan's syndrome, neuromyotonia, neuropathic pain Thymoma GABAB receptor Ataxia, OMS, chorea LE SCLC GABAA receptor OMS, SPS, chorea Status epilepticus, LE Thymoma, SCLC mGluR1 Ataxia Seizures, cognitive impairment Hodgkin Lymphoma, renal cancer VGCC Ataxia Lambert‐Eaton syndrome SCLC DPPX PERM, OMS, tremor, ataxia Behaviour changes, cognitive decline, seizures, dysautonomia, diarrhoea, weight loss B cell neoplasms IgLON5 Chorea, parkinsonism, ataxia, limb stiffness, dystonia Non‐REM and REM‐sleep disorder, stridor, bulbar symptoms, cognitive impairment, eye movement abnormalities Not reported Glycine receptor SPSD Seizures, encephalopathy Thymoma, lymphoma, SCLC, breast cancer Dopamine 2 receptor Chorea, dystonia, parkinsonism, tics Psychiatric disturbances Not reported Neurexin‐3α Orofacial dyskinesias Confusion, seizures, decrease level of consciousness Not reported Intracellular antigens Amphiphysin SPSD SCLC, breast cancer GAD65 SPSD, ataxia LE, epilepsy Rare: thymoma, lymphoma, breast cancer, other CRMP5 Chorea, ataxia, OMS LE, encephalomyelitis, neuropathies SCLC, thymoma Ma2 OMS, parkinsonism LE, brain stem encephalopathy Testicular cancer Ri Jaw dystonia, ataxia, OMS, parkinsonism Brain stem encephalopathy SCLC, breast cancer Yo Ataxia Ovarian cancer, breast cancer Hu Ataxia LE, polyneuropathy, brainstem encephalopathy, pseudoathetosis SCLC Tr/DNER Ataxia Hodgkin Lymphoma GFAP Tremor, ataxia Encephalopathy, meningitis, myelopathy, seizures, dysautonomia, psychiatric Ovarian teratoma, prostate adenocarcinoma NMDA, N‐methyl‐d‐aspartate; LGI1, leucine‐rich glioma‐inactivated 1; CASPR2, contactin‐associated protein‐like 2; GABAA/B, gamma‐aminobutyric acid A/B; mGluR1, metabotropic glutamate receptor type 1; VGCC, voltage gated calcium channel; DPPX, dipeptidyl‐peptidase‐like protein‐6; GAD, glutamic acid decarboxylase; CRMP5, collapsin‐response mediated protein 5; GFAP, glial fibrillary acidic protein; SCLC, small cell lung cancer; LE, limbic encephalitis; SPS, stiff person syndrome; SPSD, stiff‐person syndrome spectrum disorder; PERM, progressive encephalomyelitis with rigidity and myoclonus; OMS, opsoclonus myoclonus syndrome; REM, rapid eye movement. The practical importance of both the antigenic specificity and the effects of immunotherapies make our understanding of the underlying immunopathology critical to managing patients with these conditions.4, 6-10 Therefore, in this review, we focus on the immunological mechanisms that are likely to initiate and propagate the diseases and outline roles for the autoantibody‐producing plasma cells, their precursor B cells, and Tcells. We also discuss the relevance of antigen‐drainage, tumors, the blood‐brain barrier and theprinciple pathogenic mechanisms by which the autoantibodies may induce disease at a molecular level(Figs. 1 and 2).1, 4, 6 This permits us to consider methods to tailor immunotherapies toward the underlying immunology. However, to ensure the accurate administration of immunotherapies, we describe these alongside the key clinical features that permit early recognition of immunotherapy‐responsive autoantibody‐mediated movement disorders.3, 5, 7 Throughout, we focus on the most common likely pathogenic autoantibodies and review those autoantibodies which potentially challenge the paradigm that targetting of surface epitopes implies causation. Inside or Outside the Plasma Membrane? Location Matters The major factor that governs the likely pathogenicity of an autoantibody response is whether it targets the intracellular versus extracellular domain of the autoantigen (Table 1 and Fig. 1). Autoantibodies directed against the extracellular domains of surface proteins (NSAbs; often termed neuroglial surface autoantibodies) are able to exert an effect on their target antigen in vivo and are therefore considered to have pathogenic potential. In contrast, autoantibodies that target intracellular antigens may never have the opportunity to bind their target.8-10 Many such autoantibodies (including Hu, Yo, Ri, CRMP5, and Ma2) are considered bystanders of an immunological process that is often mediated by pathogenic CD8 (cluster of differentiation) T cells.11, 12 These autoantibodies are frequently associated with tumors and are summarized in Table 1 and previous reviews.3, 13 Indeed, unlike NSAb‐related disorders,14 the passive transfer of intracellular‐directed autoantibodies to experimental animals has failed to reproduce features of the disease.15 Furthermore, it may be predicted that if driven by a dominant CD8 T cell response, the human disease should benefit from drugs directed to inhibit T cell function and, indeed, sirolimus has been shown to somewhat improve functional outcomes in these disorders that typically have a very poor prognosis.16 In addition, a hinterland category exists of antigens that may transiently reach the cell surface, such as those directed at the synaptic vescicle protein glutamic acid decarboxylase (GAD, Fig. 3). Here, exposure to the extracellular compartment may occur during vescicle fusion and potentially account for an effect on the intracellular antigenic target.8 Alternatively, they may represent an immune epiphenomenon that is sometimes detectable alongside, currently largely unidentified, coexistent NSAbs.17 In addition, antibodies to the voltage‐gated potassium channel complex that do not target leucine‐rich glioma‐inactivated‐1 (LGI1) or contactin‐associated protein‐like 2 (CASPR2) are directed against intracelluar epitopes and, associate with a broad, diverse, and seemingly unrelated set of neurological conditions.18 Therefore, these clinically‐irrelevant ‘double‐negative’ voltage gated potassium channel complex antibodies will not be discussed further herein. Treatment Principles Unlike most of those with solely intracellular‐directed autoantibodies, patients with NSAbs often show a good response to first‐line therapies such as corticosteroids, intravenous immunoglobulins, and plasma exchange.19-21 Patients with GAD antibodies can also show a response to many of these treatments, but overall this cohort is more refractory to available agents. However, in all patients, the upscaling of immunotherapies to second‐line treatments—such as cyclophosphamide and rituximab—should be instigated in those refractory to the first‐line therapies. This up‐titration should be quicker in patients whose disease is more severe, often within 2 weeks in N‐methyl‐d‐aspartate receptor (NMDAR)‐antibody encephalitis. Also, there are increasingly strong data to support the generic notion that early treatments improve clinical outcomes19, 21-25; hence, therapies should be ideally instigated on the basis of a clinical diagnosis while awaiting confirmatory serology. Therefore, in this review, we emphasize highly distinctive clinical features within the autoantibody‐associated movement disorders and use the aforementioned framework to reflect on the underlying mechanistic neuroimmunology as a basis to guide current and future immunotherapy options. The NSAb‐Mediated Syndromes and Their Related Immunology NMDAR Antibodies Clinical Features The discovery of autoantibodies against the GluN1 (NR1) subunit of the NMDAR identified a diffuse encephalitis with early psychiatric and cognitive features.19, 24-26 The associated characteristic hyperkinetic movement disorder is typically recognized after about 1 to 2 weeks, commonly involves the face, limbs, and trunk and has been variably described as dyskinetic orchoreoathetoid.24, 25, 27, 28 However, a recent study has suggested a more complex, combinatorial nomenclature may be most appropriate with expert raters noting the highly‐distinctive combination of dystonia, chorea and stereotypies with a paucity of tremor or myoclonus in many patients (Fig. 3C).29 Accompanying agitation may alternate with periods of catalepsy and catatonia and sometimes a hypokinetic phenotype can predominate, resembling endophenotypes of encephalitis lethargica.30 Treatment In NMDAR‐antibody encephalitis, around 50% of patients respond to first‐line medications, usually with a good recovery over several weeks to months.19, 24 However, in this condition, their use may be limited by agitation and behavioral difficulties. This is especially true of plasma exchange, which requires significant patient compliance. Hence, it is sometimes necessary to sedate patients to permit administration of these first‐line therapies. For patients who are refractory to these drugs, rituximab and/or cyclophosphamide are recommended second‐line options, and there are data to suggest that their administration is associated with improved outcomes.19, 22, 24, 25 Throughout, early removal of the ovarian teratoma should be a therapeutic goal. As recent laboratory observations may explain some of these clinical findings,31-33 we next discuss the immunology in the context of the therapeutic data. Immunology NMDAR‐antibody encephalitis is associated with 2 known immunological triggers: an ovarian teratoma and preceding herpes simplex virus encephalitis (HSVE). Although in patients with intracellular directed autoantibodies tumors are often malignant, the ovarian teratoma in patients with NMDAR antibodies is typically benign. The teratoma, seen in about 20% of adults and few children,24, 25, 30 is likely to be a site of immunization as it contains dense infiltrations of T cells and B cells31 and its removal can hasten recovery.19, 24 Indeed, a recent paper showed that lymphocytes—both B cells and plasma cells—within the teratoma have the capacity to produce NR1‐directed autoantibodies, and the cystic teratoma fluid contains higher levels of NMDAR‐antibodies than serum.31 By contrast, the mechanism of NMDAR‐antibody encephalitis post‐HSVE is less clear.34-36 Typically, this disorder begins around 4 to 8 weeks after onset of HSVE at a time where patients, mainly children, are improving from the HSVE. Children often present with prominent choreoathetosis, abnormal behavior, and cognitive impairment: this syndrome appears identical to a primary NMDAR‐antibody encephalitis and distinctive from a relapse of HSVE.37 In adults, a similar pathophysiological phenomenon is observed but is not associated with a clear clinical relapse, rather a prolonged cognitive syndrome associated with a lower rate of abnormal movements.38, 39 Mechanistically, the necrotic disease process of HSVE may release a variety of neuronal antigens, including neuronal surface proteins. This may be more prominent after HSVE and other viruses, by comparison to traumatic brain injury, stroke, or neurodegeneration40 due to the more inflammatory environment or direct effects of viruses on lymphocytes.41 Subsequently, released antigen may be soluble or taken up by antigen‐presenting cells that migrate to cervical lymph nodes, the secondary lymphoid organs known to drain CNS lymphatics.42 Presentation of this antigen to T cells can lead to consequent B cell activation and antibody production in lymph node germinal centres (Figure 2). Consistent with this interaction, interruption of germinal center reactions with ongoing T cell and B cell interactions may explain the benefits of early and rapidly escalated immunotherapies including corticosteroids, cyclophosphamide, and rituximab.19, 24, 25, 43 Indeed, circulating B cells from patients with NMDAR antibody encephalitis can produce NMDAR antibodies in vitro, especially under conditions that mimic T cell help.31 Methods to determine the degree and nature of T and B cell involvement may in future help predict the value of cell specific therapies: for example, the autoantibodies can be transiently removed with plasma exchange, B cells deleted with rituximab, and the T cells inhibited with drugs such as cyclophosphamide. In terms of autoantibody generation mechanisms, molecular mimicry between HSV‐associated antigens and the NMDAR seems unlikely as other CNS viruses, such as varicella zoster, have been shown to trigger NMDAR‐antibody encephalitis.44 By analogy, we have also observed NMDAR‐antibody encephalitis after other viral and idiopathic neurological inflammatory illnesses (Irani and Leite, 92). In addition, there is often the concomitant presence of other antigen‐specific NSAbs, such as those against the dopamine 2 receptor, gamma‐aminobutyric acid type A receptor (GABAAR) and other unknown targets, after HSVE.35, 45 Finally, no viral epitope has been reported with sequence homology to the NMDAR. Rather, this array of autoantibody specificities post‐HSVE is likely to reflect the concept of epitope spread, where, in an inflammatory milleu, there is a polyclonal immune response against a range of antigens exposed after a single inciting event. However, given that most patients have neither preceding HSVE nor a teratoma and this idiopathic group have the highest relapse rate,19, 24 the most common immunological triggers of this condition have clinical importance and await discovery. One such trigger may be genetic, perhaps a HLA predisposition, particularly given the known nonwhite racial bias of this condition.24, 46 By contrast to emerging data about the cellular immunology, the autoantibodies themselves have been relatively well characterized. Their principle mechanism of action appears to be the downregulation of surface NMDARs. This leads to a direct reduction infunctional NMDARs and, in addition, may have consequences for the stability and function of other neighboring synaptic and extrasynaptic proteins.25, 47 Furthermore, although the NMDAR antibodies are of the complement‐fixing IgG1 subclass, the available brain pathology does not show complement deposition.24, 48 Complement induction often causes tissue necrosis. Hence the absence of complement deposition, alongside established functional effects of the autoantibodies, may explain the substantial reversibility and limited atrophy observed in this condition after immunotherapy.19, 24, 25 LGI1 Antibodies Clinical Features Faciobrachial dystonic seizures (FBDS) are stereotyped, frequent, and brief dystonic movements consistently associated with LGI1 antbodies (see Supporting Information Video). They predominantly involve the arm and the ipsilateral face, and less commonly the leg or the trunk.20, 21, 49 As the attacks are rarely associated with disturbance of consciousness or ictal EEG changes, they may be considered to lie in a borderland between movement disorders and seizures.50 However, and consistent with seizures, FBDS can be preceded by sensory auras and automatisms, and both agitation and speech arrest are described during or after the episodes.20, 49 Nevertheless, the semiology of FBDS is very different to that of more typical frontal and temporal lobe epilepsies. The attacks show a limited response to antiepileptic drugs, and multimodal radiological involvement of the basal ganglia is frequently observed in patients with FBDS (Fig. 3A).20, 49, 51, 52 Therefore, the origin of FBDS, and their preferred classification as a movement disorder or an epilepsy, is still debated, but pragmatically FBDS certainly continue to present to movement disorder neurologists, amongst others. Importantly, although FBDS were originally observed in the context of marked cognitive impairment (as part of an “encephalitis”), several patients present with FBDS alone. Furthermore, the relatively dramatic response of FBDS to immunotherapies, and their onset preceding the development of cognitive impairment, led to the hypothesis that their effective cessation may prevent the occurrence of cognitive impairment associated with limbic encephalitis.20, 49 Indeed, in a recent cohort of 103 patients with FBDS, this appeared to be the case, with cognitive impairment appearing frequently, and almost exclusively, in patients with ongoing FBDS.21 This may also be true of other seizure semiologies in patients with LGI1‐antibodies, which are well‐recognised and also very frequent.53-55 Moreover, as generalized chorea can sometimes precede the onset of LGI1‐antibody encephalitis, perhaps a similar paradigm also operates in this clinical scenario.56, 57 Treatment Therefore, after a clinical diagnosis is made, and by analogy to NMDAR antibodies, early immunotherapy appears to be key to outcome optimization.21 Timing is especially critical in this condition as there has been a demonstrable reduction in the probability of seizure cessation with each day of delay to immunotherapy, and because the effective treatment of FBDS may prevent cognitive impairment. In this condition, there are surprisingly limited data to suggest a benefit of rituximab.58 However, to date, early treatment with rituximab has not been systematically reported, nor have studies using medications including cyclophosphamide or bortezomib. Immunology The highly consistent association between a distinctive clinical phenotype and the presence of LGI1 antibodies strongly suggests that they have a pathogenic role. This has been strengthened by in vitro data that implicate alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐receptors and potassium channels in the downstream mechanisms of LGI1‐modulation induced neuronal dysfunction.10, 59, 60 Other functional effects of the LGI1 autoantibodies include the downregulation of the LGI1 complex, which includes LGI1's natural binding partners a disintegrin and metalloproteinase domain‐containing protein 22 and 23 (ADAM22/23).21 In addition, and by contrast to the NMDAR‐directed antibodies, LGI1 antibodies are mainly of the IgG4 subclass.21, 61 However, the LGI1‐IgG1 antibodies appear to correlate with disease severity, perhaps as they have the potential to deposit complement in the brain, as observed from some postmortem tissues.21, 62 Although tumors and prodromal infections have not been consistently observed in patients with LGI1 antibodies, the recent description of an almost universal HLA‐DRB1*07:01 allele strongly implicates a role for T cells in disease pathogenesis.63, 64 These LGI1‐specific T cells are likely to interact with B cells in peripheral germinal centers. CASPR2 Antibodies Clinical Features Antibodies against the juxtaparanodal protein CASPR2 are associated with a variety of movement disorders including neuromyotonia, chorea, ataxia, and a syndrome of orthostatic myoclonus.3, 65 Many of these typically occur in the context of an encephalopathy that is similar to that associated with LGI1 antibodies. Indeed, although neuromyotonia is often thought to occur as an isolated phenomenon, it is intriguing that many patients have additional autonomic and CNS features, suggesting a frequently more diffuse neuronal disease process.66 Treatment The management of CASPR2‐antibody conditions has received little attention to date.67-69 Our experience suggests that the ataxia and encephalopathy are usually responsive to similar therapeutic approaches as for patients with LGI1‐antibody encephalitis (Irani, Jacob, & Leite, 2017). Immunology As with LGI1 antibodies, one plausible mechanism of CASPR2‐antibody‐induced hyperexcitability is interference with the tightly CASPR2‐complexed juxtaparanodal potassium channels.10 This mechanism has been suggested by human models of CASPR2 mutations and was recently confirmed in animals receiving CASPR2‐IgG.70 In terms of autoantibody generation, CASPR2 antibodies are often associated with a thymoma, particularly in patients with neuromyotonia and Morvan's syndrome,61 and this frequent clinical observation may implicate defective central tolerance checkpoints that permit autoreactive T cells to escape into the periphery and facilitate antigen‐specific autoimmunity. In addition, 50% of patients with CASPR2‐antibodies have a recently described HLA (human leucocyte antigen)‐DRB1*11:01 association, which contrasts to the HLA‐DRB1*07:01 allele observed in patients with LGI1‐antibodies.64 Aquaporin‐4 (AQP4) and Myelin Oligodendrocyte Glycoprotein (MOG) Antibodies Clinical Features Another distinctive paroxysmal phenomenon is the tonic spasms observed in neuromyelitis optica spectrum disorders (NMOSD). Tonic spasms occur more frequently in NMOSD than multiple sclerosis71 and consist of recurrent, painful, asymmetrical dystonic posturing, typically in one or more limbs, that usually last a few seconds to minutes and occur at high frequency.72 Occasionally, they can be preceded by a sensory aura and frequently they are triggered by hyperventilation, tactile stimuli, or voluntary movements. Typically, patients have a favorable course with a rapid response to anticonvulsant drugs. Patients with the more recently described MOG antibodies typically associate with phenotypes of optic neuritis, longitudinally extensive myelitis, and acute disseminated encephalomyelitis.73 Although the latter often shows basal ganglia and thalamic imaging changes, there are only rare descriptions of movement disorders in patients with MOG antibodies in addition to the few with ataxia.74 Treatment AQP4‐antibody‐mediated NMOSD is a chronic, naturally relapsing condition. Although immunotherapy efficacy has not been explored alongside a placebo arm, to date it appears that rituximab, azathioprine, and mycophenolate mofetil all reduce relapse rates by around 60% to 70%.75, 76 Furthermore, the avoidance of several agents with proven efficacy in multiple sclerosis is important in NMOSD as they can promote NMOSD relapses.77 The longer term treatment of MOG‐antibody‐mediated diseases has only recently been investigated, and it was revealed that a corticosteroid duration of less than 6 months is associated with a higher rate of relapses.73 Immunology The astrocytopathy associated with NMOSD is characterized by autoantibodies directed against AQP4, a water channel expressed on the astrocyte end‐foot processes. These autoantibodies can induce complement deposition, AQP4 internalization, and cointernalization of the glutamate transporter excitatory amino acid transporter‐2 (EAAT2).78 The deposition of complement is marked in tissue from patients with NMOSD and is a likely explanation as to why the relapses can produce severe disability. Indeed, a recent study using the monoclonal antibody eculizumab, which neutralizes the C5 complement component, has shown striking efficacy.79 By contrast to AQP4 antibodies, the initial pathology induced by MOG antibodies occurs on oligodendrocytes, and the downstream mechanisms are currently under active investigation. IgLON5‐Antibody Associated Neurodegeneration Clinical Features Patients with Iglon5‐autoantibodies mostly present with a chronic history of a rapid eye movement sleep behavior disorder with a distinctive non–rapid eye movement parasomnia plus bulbar involvement, dysautonomia, stridor, and hypoventilation.4 The main movement disorder described is chorea, but a few cases with postural instability and a supranuclear vertical gaze palsy had a phenotype resembling progressive supranucelar palsy (PSP), and the clinical spectrum continues to expand with the recent inclusion of myoclonus, myorhythmia, and dystonia.80, 81 Immunology IgLON family member 5 (IgLON5) antibodies are found in the serum and CSF of patients with postmortem evidence of a tauopathy. This finding highlights a novel relationship between autoimmune and degenerative disorders.81 IgLON5 antibodies bind the extracellular domain of their target neuronal protein and avidly label live neurons in culture. Furthermore, these patients have a consistent HLA‐DQB1*0501 and HLA‐DRB1*1001 genotype association. However, the phenotype and histology are highly suggestive of a neurodegenerative process. Brain pathology shows neuronal loss and extensive deposits of hyperphosphorylated tau protein predominantly in the hypothalamus and the brain stem tegmentum, with a different distribution from other tauopathies. Treatment Although initial reports described a universally poor outcome after immunotherapy, with death a common outcome,81, 82 more recent work reports a relatively frequent response to immunotherapies.80 It may be that earlier recognition of this condition portends a promising outcome with immunotherapies. In summary, this distinctive tauopathy is associated with NSAbs and a clear HLA association and may be a paradigm for the future study of the immune system leading to neurodegeneration. If so, it may yet be that all known NSAbs are pathogenic. Indeed, in the other NSAb‐associated diseases discussed previously, the autoantibodies are also very likely to be causative. Hence, knowledge of the location and subsets of B cells that produce these autoantibodies has biological and therapeutic relevance.31, 83 Therefore, next we use conventional immunological paradigms to help describe and model mechanisms of antigen‐specific autoantibody generation in these conditions and link these to current and future immunotherapies. The Therapeutically Relevant Immunology Identifying the autoantibody‐producing cells has important potential implications for considering future individualized therapies because, as shown in Figure 2, through the B cell lineage there are different sets of expressed surface markers. These markers alter as originally naïve B cells encounter T cell help and antigen, and differentiate into class‐switched IgG‐positive memory B cells.84, 85 Spatial requirements for these interactions are met in germinal centers, and this interaction involves a number of T and B cell molecules—both inhibitory and stimulatory—that regulate the intensity of this reaction.86 In humans, this balance is well exemplified by the appearance of autoantibody‐mediated neurology after administration of T cell–directed checkpoint inhibitors.87, 88 Therefore, even in the most well‐established NSAb‐mediated diseases, an isolated contribution of B cells is unlikely, and there should be more consideration given to therapies targeting both T cells and B cells. Successfully activated B cells will typically undergo successive rounds of interactions with antigen and T cells until they acquire high‐affinity antibodies. Subsequently, these activated B cells may differentiate into antibody secreting cells in circulation (plasmablasts), where importantly they downregulate CD20, the target of rituximab.89 The plasmablasts which reach bone marrow niches have also often downregulated CD19 and expressed CD138.90 One important question is the degree to which these now long‐lived bone marrow resident plasma cells produce the autoantibodies.85 If they are major producers of autoantibodies, patients should be sensitive to drugs such as bortezomib, which target the proteasome—an organelle that is highly active in plasma cells. Indeed, early observational studies suggest a possible, albeit limited, response to bortezomib.91 Conversely, rituximab should have little impact as these cells are CD20 negative. Yet there is evidence that several such syndromes can respond to CD20‐targeted medications.19, 76, 58 Therefore, further careful clinic‐immunological studies are required to highlight the relative roles of these therapies and their effect on B cell subsets and autoantibody levels: these will better inform our understanding of disease immunobiology.31-33, 83 It may be that combinations of plasma cell depleting agents plus removal of precursor B cells are required to effectively remove autoreactive capacities from the B cell lineage. However, it is not solely the lymphocyte surface markers that provide therapeutically tractable drug targets. There are increasing examples where pharmacological manipulation of the cytokine and chemokine signalling pathways produce therapeutic efficacy. For example, B cells and antibody‐secreting cells are known to show dependence on Interleukin 6 (IL‐6) for survival. Indeed, inhibition of the IL‐6 receptor with tociluzimab has some proven benefit in both NMOSD and NMDAR‐antibody encephalitis.93, 94 Perhaps this line of inquiry will generate further targets to which there are already available modulators. As causative autoantibodies are consistently, albeit not universally, found in the CSF, one possibility is disease initiation and propagation by a primary intrathecal response: a hypothesis that does not involve peripheral lymph nodes. This is strongly mitigated by the consistent observation of serum autoantibodies in all of these conditions, including NMDAR‐antibody encephalitis post‐HSVE, typically at concentrations far in excess of the CSF autoantibodies.1, 10, 24, 34, 95, 96 In addition, the universal observation of peripheral, likely immunizing, systemic tumors also mitigates this possibility. More plausible is the notion of an initiating peripheral immunization. Perhaps in a manner akin to HSVE, many CNS‐restricted antigens reach the periphery via CNS lymphatics and draining cervical lymph nodes (Fig. 2).42 The constitutive versus active nature of this drainage requires further investigation as it may determine the probability of a CNS lesion initiating a peripheral immunization. Subsequent to the immunization, at least some of the peripheral response must transfer to the CNS to mediate a brain disease. One outstanding question is whether this is principally mediated by migration of the B cells or the soluble antibodies across the blood‐brain or blood‐CSF barrier. This distinction may alter clinical management strategies; for example, natalizumab will block lymphocyte trafficking across the blood‐brain barrier. Several clues exist to help us understand the nature of the brain‐based immune response. Animal studies lend support to the intuitive notion that the brain‐expressed antigens can act as a “sink” for CNS‐transferred serum autoantibodies resulting in undetectable CSF autoantibody levels.97 Indeed, although CSF LGI1 antibodies are present in most patients, they are undetectable in some cases,96, 98 and this balance may represent a saturation point of the “sink.” By contrast, in patients with NMDAR‐antibody encephalitis, the presence of autoantibodies in CSF is a requirement for definitive diagnosis.99 However, serial measurements of CSF or serum autoantibody levels in all of these conditions only broadly correlate with clinical outcomes,19, 20, 100 and perhaps other, many as yet undetermined, factors including cytokines, complement and even other autoantibody reactivities,33 together contribute to the overall clinical status. In addition to diffusion alone, there is often marked intrathecal synthesis of the NMDAR antibodies and, indeed, NMDAR‐autoantibody secreting cells within the CNS have recently been isolated by single‐cell cloning techniques.33 Therefore, the intrathecal retention of antigen‐specific cells appears necessary for generation of NMDAR‐antibody encephalitis and may be mediated by the high CSF levels of the B cell and plasma cell chemokine (C‐X‐C motif) ligand 13 (CXCL13).32 These observations, coupled with the highly heterogeneous phenotypes of patients with NMDAR antibodies in serum but not CSF,40, 101, 102 may suggest that the predicted natural diffusion of NMDAR‐IgG into the CNS is insufficient to generate this encephalitis phenotype. Yet, maybe the soluble autoantibodies do play a role in ongoing disease as plasma immunoabsorption of IgG leads to a fall in CSF autoantibodies and correlates with improvements in clinical status.103 The relative contributions of serum autoantibody transfer into the CNS and the degree of immune cell infiltration may vary across diseases but also within diseases, and could determine the likelihood of amelioration with plasma exchange or predict the need for future intrathecal‐directed therapies. Autoantibodies Against Glutamic Acid Decarboxylase 65 (GAD65), an Intracellular Synaptic Protein: Syndromes, Immunology, and Treatments In contrast to the NSAb‐mediated disorders, those associated with autoantibodies directed against intracellular targets are generally considered nonpathogenic. Indeed, as discussed previously, passive transfer and active immunization experiments have proven that some of these autoantibodies do not cause neurological diseases.104 However, the spectrum of disorders associated with autoantibodies against GAD65 and amphiphysin may challenge this notion from clinical and laboratory perspectives.105, 106 Here, we discuss the GAD‐antibody syndromes, with prominent movement disorders, in greater detail. Clinical Features Antibodies against the intracellular enzyme GAD65 are very frequently detected in stiff person syndrome and related disorders (stiff person spectrum disorders [SPSD]). This group of disorders share the hallmark features of fluctuating muscle stiffness with superimposed spasms and hyperekplexia (an excessive startle response to acoustic or tactile stimuli).107 Classic stiff person syndrome involves stiffness of the lower back and proximal leg muscles with characteristic hyperlordotic posturing. In focal forms of SPSD, stiffness may be restricted to 1 limb (stiff limb syndrome).108 Other variants of SPSD are defined by the presence of additional neurological signs such as cerebellar ataxia. Progressive encephalomyelitis with rigidity and myoclonus typically designates the severe end of the spectrum, characterized by prominent hyperekplexia and myoclonus, generalized stiffness, brain stem signs, and dysautonomia.109 Immunology Including Coexistent NSAbs High concentrations of GAD65 antibodies associate with a limited set of clinically distinctive phenotypes, namely: SPSD, cerebellar ataxia, epilepsy and limbic encephalitis (Fig. 3B), suggesting some syndrome specificity.107, 110, 111 In addition, several patients with GAD65 antibodies do respond to immunotherapy. Also, by comparison to patients with Hu‐ or Ma2‐antibody‐associated encephalitis, patients with GAD65‐antibody encephalitis showed lower CD8/CD3 ratios, indicating an appropriate designation of GAD65 antibodies between other intracellular autoantibodies and NSAbs.62 These collective observations lead to the intriguing notion that GAD65 antibodies may have some causative potential. Indeed, the closely related amphiphysin antibodies, typically associated with paraneoplastic stiff person syndrome, have been shown to both reproduce disease upon transfer to experimental animals, and they may gain access to their intracellular antigenic target.8, 106, 112 Alternatively, maybe the GAD65 antibodies coexist with NSAbs that target the extracellular domains of antigens at GABAergic and glycinergic inhibitory synapses, such as the alpha 1 subunit of the glycine receptor (GlyRα1), and GABAAR.3, 105-107 Furthermore, another NSAb found in some SPSD patients is directedagainst dipeptidyl‐peptidase‐like protein‐6 (DPPX),113, 114 a regulatory subunit of Kv4.2 potassium channels. Perhaps these coexistent autoantibodies, often with antigens expressed in the same neurons, implicate epitope spread as a mechanism to diversify the polyclonal immune responses after a triggering event that exposes several antigens to the immune system. Indeed, it appears that these coexistent NSAbs confer even more disease specificity: for example, Glycine Receptor (GlyR) antibodies frequently associate with progressive encephalomyelitis with rigidity and myoclonus and DPPX antibodies with a distinct phenotype of truncal stiffness, prominent hyperekplexia, and cerebellar ataxia.113 Both GlyR and DPPX are surface expressed, and the respective NSAbs are likely to be pathogenic, with in vitro evidence they induce antigen internalization.109, 114 Treatment Consistent with the aforementioned paradigm of intracellular antibodies versus NSAbs, from patients with SPSD the treatment responses appear better in patients with GlyR antibodies than GAD65 antibodies alone.115 The treatment with the only proven randomized clinical data within the conditions discussed in this review is intravenous immunoglobulins in SPSD.116 Patients often show a moderate benefit from this drug, but longer term alternatives are yet to be satisfactorily explored. Future Directions Given that our understanding of the immunology underlying NSAb‐mediated diseases remains in its infancy, this appears to be an important avenue for future study. Available data have led researchers to consider drugs that appear biologically intuitive, but it is yet to be seen if we can achieve disease specificity. There are some potential reasons to maintain optimism in the potential for precision medicine. First, the generation of patient‐derived monoclonal antibodies in some of these conditions offers a method to directly out‐compete the endogenous patient antibodies.117 Of course, this comes with a series of potential immunological hazards, but it would form an elegant method to test the hypothesis of whether the antibodies are the major disease perpetrators. Other options in the pipeline include the use of selective cytokine and chemokine blockade. For example, in NMDAR‐antibody encephalitis, raised CSF levels of CXCL13 have been proposed as an intrathecal lymphocyte chemoattractant. Their neutralization may inhibit lymphocyte crossing. However, if this were effective, it may yet require a parallel peripheral depletion of B cells to adequately extinguish the disease. Indeed, this combinatorial approach may be a future theme in these increasingly complex diseases that require collaborations of at least T cells and B cells. One such vision may by combinatorial assessment of the autoantibody production from patient lymphocytes under a large number of cytokine conditions31, 83 and then block the dominant culprit pathways with targeted monoclonal therapies. Such an approach would be patient specific, especially if complemented by evaluation of endogenous cytokine levels, but if generic stimuli expanded these B cells, this approach may be intrinsically limited. Given recent advances in the clinical immunology,31, 83, 93 future studies should be able to answer these possibilities rapidly. Conclusions The increasing numbers of identified neuronal autoantibodies are associated with a broadening clinical spectrum of autoantibody‐mediated movement disorders. This contemporary expansion makes the field increasingly important for the movement disorder specialist and for the general neurologist. This is particularly the case given the recognition that early immunotherapy is likely to improve prognosis and prevent the ongoing pathogenic effects of the autoantibodies. However, to understand the root causes of these illnesses, the field requires an improved future understanding of the varied roles of immune components—including T cells, B cells, plasma cells—and their associated surface markers. Indeed, many of the conventional immunological paradigms as outlined require confirmation with the direct study of these diseases. In addition to biological insights, this may offer a method to specifically target causative cell types in these diseases. The relative roles of these different immune components may vary in conditions with intracellular versus surface autoantibodies and depend on the inciting factor in the autoantibody‐mediated conditions. Furthermore, the degree to which reduction in T cell function or autoantibody level is required to achieve clinical improvement should be considered as many of these autoantibodies can persist for years despite good clinical remission.20, 24, 118 Therefore, to move toward precision medicine in these conditions, there is an urgency to better appreciate the immunological mechanisms that underlie the generation and perpetuation of the autoantibodies, and this may lead to novel therapeutic strategies that could be addressed in clinical trials. Author Roles 1) Research project: A. Conception, B. Organization, C. Execution; 2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3) Manuscript: A. Writing of the first draft, B. Review and Critique. V.D.: 1A, 1B, 1C, 3A, 3B B.B.: 1A, 1B, 1C, 3A, 3B A.K.K.: 1B, 1C, 3B S.R.I.: 1A, 1B, 1C, 3A, 3B Full financial disclosure for the previous 12 months SRI is a coapplicant and receives royalties on patent application WO/2010/046716 (U.K. patent no., PCT/GB2009/051441) entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC‐complex antibodies. Supporting Information References Notes : 1 Valentina Damato and Bettina Balint contributed equally. Funding agency: S.R.I. is supported by the Wellcome Trust (104079/Z/14/Z), BMA Research Grants‐Vera Down (2013) and Margaret Temple (2017) Grants, Epilepsy Research UK (P1201), and by the Fulbright UK‐US commission (MS‐society research award). The research was funded/supported by the National Institute for Health Research Oxford Biomedical Research Centre (BRC; the views expressed are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health). B.B. is supported by the EAN research fellowship program and by Robert Bosch Stiftung. Relevant conflicts of interests/financial disclosures: S.R.I. is a coapplicant and receives royalties on patent application WO/2010/046716 titled “Neurological Autoimmune Disorders.” The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC‐complex antibodies. NMDA, N‐methyl‐d‐aspartate; LGI1, leucine‐rich glioma‐inactivated 1; CASPR2, contactin‐associated protein‐like 2; GABAA/B, gamma‐aminobutyric acid A/B; mGluR1, metabotropic glutamate receptor type 1; VGCC, voltage gated calcium channel; DPPX, dipeptidyl‐peptidase‐like protein‐6; GAD, glutamic acid decarboxylase; CRMP5, collapsin‐response mediated protein 5; GFAP, glial fibrillary acidic protein; SCLC, small cell lung cancer; LE, limbic encephalitis; SPS, stiff person syndrome; SPSD, stiff‐person syndrome spectrum disorder; PERM, progressive encephalomyelitis with rigidity and myoclonus; OMS, opsoclonus myoclonus syndrome; REM, rapid eye movement.
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The Anti-NMDA Receptor Encephalitis Foundation Newsletter

The Anti-NMDA Receptor Encephalitis Foundation Newsletter | AntiNMDA | Scoop.it
Admission diagnoses of patients later diagnosed with autoimmune encephalitis.– PubMed – NCBI From...
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Anti-NMDAR Encephalitis: The root of demonic possessions? –

Anti-NMDAR Encephalitis: The root of demonic possessions? – | AntiNMDA | Scoop.it
Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis, a disease in which the body attacks the brain, was first discovered in 2007, and has been characterized by many as the possible root of…...
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Neuropsychological And Psychopathological Profile Of Anti-Nmdar Encephalitis: A Possible Pathophysiological Model For Pediatric Neuropsychiatric Diso... - PubMed - NCBI

Neuropsychological And Psychopathological Profile Of Anti-Nmdar Encephalitis: A Possible Pathophysiological Model For Pediatric Neuropsychiatric Diso... - PubMed - NCBI | AntiNMDA | Scoop.it
Arch Clin Neuropsychol. 2018 Nov 12. doi: 10.1093/arclin/acy088.[Epub ahead of print]...
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A case of NMDAR encephalitis misdiagnosed as postpartum psychosis and neuroleptic malignant syndrome - ProQuest

A case of NMDAR encephalitis misdiagnosed as postpartum psychosis and neuroleptic malignant syndrome Koksal, Ayhan; Baybas, Sevim; Mutluay, Belgin; Altunkaynak, Yavuz; Keskek, Asli. Neurological Sciences; Milano Vol. 36, Iss. 7,  (Jul 2015): 1257-1258. DOI:10.1007/s10072-014-1966-3
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Autoimmune encephalitis with psychosis: Warning signs, step-by-step diagnostics and treatment. - PubMed - NCBI

Autoimmune encephalitis with psychosis: Warning signs, step-by-step diagnostics and treatment. - PubMed - NCBI | AntiNMDA | Scoop.it
World J Biol Psychiatry. 2018 Dec 4:1-25. doi: 10.1080/15622975.2018.1555376.[Epub ahead of print]...
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Anti-NMDA Receptor Encephalitis Foundation Travel Award 2019

Anti-NMDA Receptor Encephalitis Foundation Travel Award 2019 | AntiNMDA | Scoop.it
The Foundation is pleased to announce its intention to offer ONE Travel Award to a Canadian medical trainee to offset costs associated with attendance at ...Read More...
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Electroconvulsive therapy for anti-N-methyl-d-aspartate (NMDA) receptor encephalitis: A systematic review of cases

Electroconvulsive therapy for anti-N-methyl-d-aspartate (NMDA) receptor encephalitis: A systematic review of cases | AntiNMDA | Scoop.it
Anti-NMDA receptor encephalitis most commonly presents with psychiatric symptoms such
as behavioural disturbance, catatonia and psychosis. Although the primary treatment
is with immunomodulatory therapy, psychiatric symptoms often require adjuvant management.
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Autoimmune Encephalitis as an Extra-articular Manifestation of Rheumatoid Arthritis: A Case Report

Japan's largest platform for academic e-journals: J-STAGE is a full text database for reviewed academic papers published by Japanese societies...
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The power of perseverance –

The power of perseverance – | AntiNMDA | Scoop.it
Niamh Cahill is an example of a strong young woman who fights for her dreams, regardless of the stormy seas...
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Anti-NMDA Receptor Encephalitis in a Young Girl with Altered Behaviour and Abnormal Movements. - PubMed - NCBI

Anti-NMDA Receptor Encephalitis in a Young Girl with Altered Behaviour and Abnormal Movements. - PubMed - NCBI | AntiNMDA | Scoop.it
J Coll Physicians Surg Pak. 2018 Aug;28(8):643-644. doi: 10.29271/jcpsp.2018.08.643.Case Reports...
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Intravenous immunoglobulin in paediatric neurology: safety, adherence to guidelines, and long-term outcome. - PubMed - NCBI

Intravenous immunoglobulin in paediatric neurology: safety, adherence to guidelines, and long-term outcome. - PubMed - NCBI | AntiNMDA | Scoop.it
Dev Med Child Neurol. 2016 Nov;58(11):1180-1192. doi: 10.1111/dmcn.13159. Epub 2016 May 31.
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Time for a change of practice: the real-world value of testing for neuronal autoantibodies in acute first-episode psychosis

Time for a change of practice: the real-world value of testing for neuronal autoantibodies in acute first-episode psychosis | AntiNMDA | Scoop.it
It is time that all patients with acute-onset psychosis are screened for autoimmune encephalitis, that lumbar puncture becomes a routine psychiatric investigation and that immunotherapy is available in indicated cases.
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Frontiers | Management of Autoimmune Encephalitis: An Observational Monocentric Study of 38 Patients | Immunology

Frontiers | Management of Autoimmune Encephalitis: An Observational Monocentric Study of 38 Patients | Immunology | AntiNMDA | Scoop.it
The emerging field of autoimmune encephalitis has gained importance over the last years in neurology. The broad field of symptoms and syndromes poses a great challenge in diagnosis for clinicians. Most important in the management of AIE is early diagnosis and based on it the appropriate treatment.
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November 21, 2018 e-Pearl of the Week: Faciobrachial dystonic seizures in LGI-1 positive autoimmune encephalitis | Neurology

November 21, 2018 e-Pearl of the Week: Faciobrachial dystonic seizures in LGI-1 positive autoimmune encephalitis | Neurology | AntiNMDA | Scoop.it
Faciobrachial dystonic seizures in LGI-1 positive autoimmune encephalitis Faciobrachial dystonic seizures (FBDS) are a pathognomonic finding in autoimmune encephalitis with anti-leucine-rich glioma-inactivated protein-1 (LGI-1) autoantibodies1, directed against a voltage-gated potassium channel complex. FBDS are brief episodes of face tightening and grimacing with unilateral or bilateral arm flexing and hand tightening2. Sometimes flexion of the leg can be present. The number of episodes may range from a few up to three hundred per day1. EEG may be normal or, less frequently, may show ictal epileptiform changes. FBDS may be the first clinical manifestation of autoimmune encephalitis and, if detected, then LGI-1 autoantibody testing from the serum and, if possible, from the cerebrospinal fluid is recommended. Response to antiepileptic therapies is usually poor, with immunomodulatory treatment typically being more effective. References 1. Irani SR, Michell AW, Lang B, et al. Faciobrachial Dystonic Seizures PrecedeLgi1 Antibody Limbic Encephalitis. Ann Neurol 2011 May;69:892-900. 2. Watson E, Rosemergy I, Taylor J, Abernethy D, Lanford J. Faciobrachial dystonic seizures in an Lgi1 VGKC-complex antibody-mediated encephalitis. Neurol Clin Pract 2015;5:536-537.   Submited by Antonino Giordano, MD, Resident in Neurology – Neurological Department, San Raffaele University Hospital. Dr. Giordano reports no disclosures.
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