AntiNMDA
26.8K views | +2 today
Follow
 
AntiNMDA
Your new post is loading...
Scooped by Nesrin Shaheen
Scoop.it!

Hope in Research: The 2021 Anti-NMDA Receptor Encephalitis Foundation Prize

Hope in Research: The 2021 Anti-NMDA Receptor Encephalitis Foundation Prize | AntiNMDA | Scoop.it
Our hope and that of our many followers lies in supporting research. In 2019 we introduced The Anti-NMDA Receptor Encephalitis Prize to support and empower ...Read More...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

"N-Methyl-D-Aspartate Receptor Antibodies in Herpes Simplex Encephaliti" by Jefin Jose

Despite the relatively-low prevalence of Herpes Simplex Encephalitis (HSE), it is among the most fatal forms of brain inflammation. In the present study, Pruss et al. seeks to determine the presence of and quantify the specific immunity towards the N-Methyl-D-Aspartate receptor (NMDAR), a synaptic...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

May and June tests

May and June tests | AntiNMDA | Scoop.it
In May and June 2021, Mayo Clinic Laboratories announced three new tests along with numerous reference value changes, obsolete tests, [...]...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Clinical and neuroimaging findings in MOGAD–MRI and OCT - Bartels - - Clinical & Experimental Immunology

Clinical and neuroimaging findings in MOGAD–MRI and OCT - Bartels - - Clinical & Experimental Immunology | AntiNMDA | Scoop.it
Abstract Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are rare in both children and adults, and have been recently suggested to be an autoimmune neuroinflammatory group...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Two de novo GluN2B mutations affect multiple NMDAR-functions and instigate severe pediatric encephalopathy

Two de novo GluN2B mutations affect multiple NMDAR-functions and instigate severe pediatric encephalopathy | AntiNMDA | Scoop.it
Two novel mutations in the GRIN2B gene reduce glutamate affinity by >1000-fold, reduce the receptors proton-sensitivity, and exert a dominant-negative effect over receptors in neurons.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Long-term Outcomes After Autoimmune Encephalitis - Dr. Anusha Yeshokumar | Building Bridges 2021

No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Prognostic Considerations in Anti-NMDA Receptor Encephalopathy With Psychiatric Manifestations

Prognostic Considerations in Anti-NMDA Receptor Encephalopathy With Psychiatric Manifestations | AntiNMDA | Scoop.it
This CME covers how CNS-related psychosis may require medical interventions beyond antipsychotic and other psychotropic medications.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

When to Suspect Autoimmune Causes for Neurologic Disorders (Podcast) –

When to Suspect Autoimmune Causes for Neurologic Disorders (Podcast) – | AntiNMDA | Scoop.it
A Cleveland Clinic expert shares the essentials of evaluating and managing encephalitis and other neurologic disorders of suspected autoimmune origin.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Hope in Research: 2021 Anti-NMDA Receptor Encephalitis Prize / Espoir en la recherche : Prix de l'encéphalite à anticorps antirécepteurs NMDA 2021

Hope in Research: 2021 Anti-NMDA Receptor Encephalitis Prize / Espoir en la recherche : Prix de l'encéphalite à anticorps antirécepteurs NMDA 2021 | AntiNMDA | Scoop.it
Our hope and that of our many followers lies in supporting research. In 2019 we introduced The Anti-NMDA Receptor Encephalitis Prize to support and empower promising new researchers, passionate about the field of neuroimmunology. We are delighted to announce this year’s winner, Dr. Julien Hébert.  Julien Hébert is a fellow in clinical neurophysiology and epilepsy at Columbia University (New York, USA). He completed his neurology residency at the University of Toronto (Canada) and medical school at McGill University (Montreal, Canada). He has obtained a Master of Science in epidemiology from Sorbonne University (Paris, France) in 2019. His Master’s thesis on the epidemiology of Autoimmune Encephalitis in France was awarded the Elsevier Best Clinical Paper Award at the World Congress of Neurology in 2020. He has been involved with the University Health Network Autoimmune Encephalitis Clinic, in Toronto, since 2016. He is passionate about caring for patients with autoimmune encephalitis and contributing to research in this field. Dr. Hébert’s research findings were published last year in an article entitled, Searching for autoimmune encephalitis: Beware of normal CSF. We are pleased to provide the following abstract to his important work: https://pubmed.ncbi.nlm.nih.gov/32563126/ We are grateful for the invaluable support of the Canadian Federation of Neurological Sciences and the Canadian Neurological Society, which is part of the federation, for hosting our prize over the past three years, at their annual Congress. We are hopeful that this year’s congress will go ahead as an in-person conference on Monday, 25 October to Thursday, 28 October in Toronto, Ontario. Here is the link to the Congress website: https://www.cnsf.org/congress/ Last but not least, we would like to thank our generous donors for their loyal support to ensure the continuity of this award.  Your continued support is greatly appreciated. https://www.antinmdafoundation.org/donate/
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Thesis defense - Frédéric Villéga

Thesis defense - Frédéric Villéga | AntiNMDA | Scoop.it
Molecular impact of the antagonist ketamine in Auto-immune encephalitis with NMDA-R Ab...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoimmune Encephalitis in First Episode Psychoses | Neurology

Autoimmune Encephalitis in First Episode Psychoses | Neurology | AntiNMDA | Scoop.it
SHARE July 06, 2021; 97 (1) EDITORIAL Autoimmune Encephalitis in First Episode Psychoses All Smoke and No Fire? View ORCID ProfileMaarten J. Titulaer, View ORCID ProfileGregory S. Day First published May 12, 2021, DOI: https://doi.org/10.1212/WNL.0000000000012195 FULL PDF CITATION PERMISSIONS MAKE COMMENT SEE COMMENTS Downloads63 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. The discovery of patients with prominent psychosis and subacute decline in neurologic function associated with immunoglobulin G (IgG) autoantibodies against CNS NMDA receptors (NMDAR) established anti-NMDAR encephalitis as a novel cause of new-onset psychoses.1 Although patients may be severely affected at presentation (earning the moniker “brain on fire”), remarkable improvement is noted after early induction of appropriate immunotherapies.2 The importance of early treatment has highlighted the need to improve recognition of patients early in the disease course when psychiatric symptoms predominate and most patients are likely to meet criteria for first episode psychoses (FEP). Footnotes Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial. See page 24 © 2021 American Academy of Neurology View 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 RELATED ARTICLES TOPICS DISCUSSED ALERT ME
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Learning to Bloom Where You're Planted | Monthly Resilience Report: June 2021 (Last One)

Learning to Bloom Where You're Planted | Monthly Resilience Report: June 2021 (Last One) | AntiNMDA | Scoop.it
Two years ago this month, I was hospitalized for the first time. I was diagnosed with seronegative autoimmune encephalitis (AE). And I started 5 months of immunotherapy, roughly 5 years after my illness first began.By November 2019, I thought the battle was won: I seemingly had all the answers to...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Frontiers | Limitations of a Commercial Assay as Diagnostic Test of Autoimmune Encephalitis | Immunology

Frontiers | Limitations of a Commercial Assay as Diagnostic Test of Autoimmune Encephalitis | Immunology | AntiNMDA | Scoop.it
Detection of neuronal surface antibodies (NSAb) is important for the diagnosis of autoimmune encephalitis (AE). Although most clinical laboratories use a commercial diagnostic kit (Euroimmun, Lübeck, Germany) based on indirect immunofluorescence on transfected cells (IIFA), clinical experience...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Cureus | N-Methyl-D-Aspartate Receptor-Negative Autoimmune Encephalitis in a Patient With an Ovarian Teratoma and an Associated Novel Cerebrospinal Fluid Autoantibody

Cureus | N-Methyl-D-Aspartate Receptor-Negative Autoimmune Encephalitis in a Patient With an Ovarian Teratoma and an Associated Novel Cerebrospinal Fluid Autoantibody | AntiNMDA | Scoop.it
Autoimmune encephalitis is most commonly caused by autoantibodies against N-methyl-D-aspartate (NMDA) receptors, and the malignancy most often associated with anti-NMDA receptor autoimmune encephalitis is an ovarian teratoma.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management | Journal of Neurology, Neurosurgery & Psychiatry

Introduction In the first part of the Proposed Best Practice Recommendations, we covered diagnosis and acute immunotherapy for autoimmune encephalitis (AE). In this second part, we will cover symptomatic, bridging and maintenance immunotherapy of AE. The recommendations are based on literature review and an online survey of 68 members of the Autoimmune Encephalitis Alliance Clinicians Network (AEACN). The final manuscript was approved by all participating members after four rounds of revisions. Please refer to part-1 (Proposed Best Practice Recommendations for Diagnosis and Acute Management) for methodology details. Symptomatic therapy AE is often polysymptomatic. Symptoms start in the acute phase and may resolve or improve with acute immunotherapy alone or combined with targeted symptomatic treatment. However, many residual symptoms persist beyond the acute phase requiring long-term symptomatic therapy. In this section, we will review symptomatic therapy in both the acute phase of the disease and the long-term. A summary of symptomatic therapy recommendations is included in table 1. VIEW INLINE VIEW POPUP Table 1 Symptomatic management for autoimmune encephalitis Management of psychosis Often benzodiazepines are required in large doses for adequate sedation. Many patients with AE will need antipsychotics to control agitation and psychosis.1 One option is to avoid agents that lower seizure threshold (eg, clozapine and olanzapine)2 in patients with seizures or who are at increased seizure risk (eg, patients with limbic or cortical encephalitis or who have lateralised periodic discharges (LPDs) on electroencephalogram (EEG)). Antipsychotics that prolong the QT interval (eg, ziprasidone and IV haloperidol) should be used with caution or avoided in dysautonomic patients with symptomatic bradycardia or heart block. If an antipsychotic results in worsening of agitation or involuntary movements after initiation, it should be stopped and substituted with an alternative agent. In NMDAR-antibody encephalitis (see online supplemental appendix 1 for full names of neuronal autoantibodies (NAAs)), patients may be particularly sensitive to the extrapyramidal side effects of antipsychotics and may experience worsening of catatonia and other involuntary movement or even develop neuroleptic malignant syndrome.3 Second generation antipsychotics with the least potential for inducing seizures and extrapyramidal side effects (eg, quetiapine) may be preferred in patients with AE. Patients with manic symptoms in the setting of AE may be treated with mood stabilisers such as valproic acid especially in case of comorbid seizures.1 Elimination or dose reduction of certain medications may also improve behavioural symptoms in some patients (eg, steroids, benzodiazepines). It is important to instate safety measures (eg, padding, soft restraints, etc) for agitated patients to prevent self-injury and harm to others. Supplemental material Management of seizures In addition to immunotherapy, patients with AE with clinical or electrophysiological seizures may require treatment with antiseizure medications effective against focal seizures.4 However, in leucine-rich glioma inactivated-1 (LGI1)-antibody encephalitis, despite there being data showing sodium-channel blockers may be the most effective antiseizure medications,5 6 it is very clear that immunotherapy is far more effective than seizure medications in general. Hence, immunotherapies should be the antiseizure medication of choice in this condition.6–9 Patients with status-epilepticus may require standard status-epilepticus protocol with fast-acting intravenous benzodiazepines followed by intravenous loading of an appropriate antiseizure medication such as fosphenytoin, valproic acid or levetiracetam. Patients with new onset refractory status-epilepticus (NORSE) will require induced coma with midazolam, pentobarbital or propofol in an intensive care unit (ICU) setting.10 In super refractory status-epilepticus, effective seizure control may not be achieved until sufficient immunosuppression is in effect. In many patients, improvement of LPDs and other EEG abnormalities may be followed by improvement in mental status. Patients may not need long-term antiseizure medications after resolution of the acute attack. The nationwide retrospective study by de Bruijn and colleagues highlighted the central role of immunosuppression in controlling AE seizures and showed that almost all surviving patients with NMDAR, LGI1 and GABA-B-R-antibody encephalitis remained seizure-free and could be weaned off seizure medications successfully after immunosuppression and resolution of brain inflammation.6 Antiseizure medications have several side effects and weaning should be considered in recovered patients with normal brain MRI and EEG. Due to medical, social and driving privilege implications, data beyond 5 years of follow-up and from all AE subtypes is still needed before making definitive generalised recommendations regarding the optimal duration of antiseizure mediations following the initial AE attack. Clinicians should practice caution and consider several factors when making this decision including the type of antibody, the severity of the initial presentation, MRI and EEG findings, tolerability of the antiseizure agent, and local and national epilepsy guidelines. Patients who present initially with NORSE may be at a higher risk for chronic epilepsy. In the largest case series of NORSE (all aetiologies) to date, 37% of patients later developed chronic epilepsy and 92% of survivors remained on antiseizure medications.11 Management of movement disorders Mild movement disorders in the setting of AE do not require specific symptomatic therapy as they may improve with immunotherapy alone. Severe, dangerous or disabling movement disorders will require phenomenology-directed treatment.12 Severe dystonia may be treated with anticholinergics or muscle relaxants (eg, trihexyphenidyl, baclofen, respectively); myoclonus, stiff person syndromeand progressive encephalomyelitis with rigidity and myoclonus can be treated with benzodiazepines; catatonia may respond to intravenous lorazepam and/or electroconvulsive therapy although the relapse rate and cognitive impact of the latter is unknown in patients with AE.1 12 Severe chorea, athetosis and ballism can be treated with a cautious use of dopamine-blockers or depleters (eg, risperidone, tetrabenazine, respectively) while carefully watching for any paradoxical worsening of other involuntary movements. Dopaminergic treatment with dopamine agonists or carbidopa/levodopa may be tried in patients with acquired parkinsonism or severe akinetic-rigid syndrome.12 Management of dysautonomia In most cases, supportive therapy with continuous monitoring in an ICU setting along with immunotherapy is all that is needed in dysautonomic patients. However, on rare occasions, symptomatic treatment with non-selective beta-blockers, alpha-2 agonists and/or acetylcholinesterase inhibitors may be required to ameliorate sympathetic overactivity. Patients with severe symptomatic postural hypotension may require midodrine, fludrocortisone or droxidopa in addition to good hydration and compressive stocking usage. Temporary pacing may be required in patients with acquired heart block or severe arrhythmias. In addition to symptomatic pharmacotherapy, patients with severe gastrointestinal dysmotility may require temporary total parenteral nutrition, and those with urinary retention often require indwelling catheters. Patients with central hypoventilation require artificial ventilation. Management of sleep dysfunction Improved sleep facilitates control over agitation, seizures and psychosis. Improving the sleep cycle is imperative in patients with AE and should be among the priorities of symptomatic therapy. The use of environmental conditioning and sleep hygiene, along with pharmacological measures such as melatonin, sedating benzodiazepines (eg, clonazepam or diazepam) and/or non-benzodiazepine hypnotics (eg, zopiclone) should be considered as appropriate for patients with AE with sleep dysfunction.3 MANAGEMENT OF ASSOCIATED NEOPLASM IF PRESENT When a paraneoplastic aetiology is confirmed, treatment of the neoplasm may result in neurological improvement or remission in some cases with or without immunotherapy.13 In cases associated with classical onconeuronal antibodies, tumour resection may be the intervention with the highest therapeutic benefit since neurological symptoms tend to be immunotherapy-resistant in many of those patients.14 In inoperable tumours, debulking surgery or palliative radiotherapy or chemotherapy may result in neurological improvement by reducing the abnormal immune drive.15 Of note, the Karnofsky Performance Status score may be poor due to the paraneoplastic syndrome rather than the direct effect of cancer so low scores should not hinder aggressive oncological management. Neurologists should consult with the appropriate oncology service and advocate for timely oncological intervention in order to expedite neurological recovery and prevent permanent neurological disability. For antibodies against neuronal surface antigens in the presence of a neoplasm, AE tends to be responsive to immounomodualting therapy but tumour treatment is still necessary for neurological improvement. For example, along with immunotherapy, resection of ovarian or testicular teratoma may accelerate remission in NMDAR-antibody encephalitis.4 Studies have shown a germinal centre-like histology of the ovarian teratomas, with intramural NMDAR-specific B-cells that can cross the blood brain and evolve into antibody-producing intrathecal plasmablasts.16–18 This suggests a plausible biological basis for the observed improvement after tumour resection. The same goes for other neuronal surface antibodies associated with various benign or malignant neoplasms like AMPA-R (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and GABA/BR antibodies. In addition to conventional antineoplastic treatments via surgical resection, chemotherapy and radiotherapy, the recent introduction of cancer-directed immune checkpoint inhibitors adds a new layer of complexity to the management of paraneoplastic AE. Although anticancer treatment usually contributes to neurological improvement, the use of ICIs is likely to trigger new paraneoplastic reactions or exacerbate pre-existing paraneoplastic AE due to the ‘unchecked’ immune response against tumour (and neuronal) antigens.19 Fortunately, the symptoms of paraneoplastic AE in the setting of ICIs are usually steroid-responsive.19 Per the recommendations of the European Society of Medical Oncology guidelines, steroids should be initiated and ICIs should be interrupted for moderate neurological side effects (grade-2) and permanently discontinued in severe cases (grade-3).20 The National Comprehensive Cancer Network guidelines consider meningitis and encephalitis as moderate or severe ICI neurotoxicity.21 If there are no other alternatives for oncological therapy, or based on patient preferences, rechallenge with ICIs may be carefully considered in selected cases after sufficient corticosteroid treatment and resolution of neurological symptoms. BRIDGING IMMUNOTHERAPY ON DISCHARGE After acute treatment, it is important to avoid abrupt discontinuation of immunotherapy to prevent early recurrence.22–24 Therefore, a bridging strategy should be implemented followed by slow weaning or initiation of long-term immunotherapy, if indicated. A common strategy is to start oral prednisone 1–2 mg/kg/day immediately after completing acute therapy followed by a gradual taper over weeks to months overlapping with long-term immunotherapy if indicated. The rate of taper varies according to the clinical syndrome, clinical context, relapse risk, and treatment response and tolerability. However, this approach may not be suitable for patients with ongoing behavioural issues or who have contraindications to maintenance corticosteroid therapy. An alternative strategy is to give periodic intravenous methyl-prednisolone (IVMP) or intravenous immunoglobulins (IVIg) as a maintenance therapy for the same duration.25 If a second-line agent such as rituximab is used during the acute attack, it may serve as a bridging therapy in itself given its long-term effects.22–24 However, corticosteroid overlap may still be needed with the initial rituximab dose to avoid possible treatment-related relapses, in alignment with reports in patients with neuromyelitis optica spectrum disorder (NMOSD)26 although AE and NMOSD are substantially different conditions. When using prednisone for extended periods of time, it is important to mitigate corticosteroids toxicity by cotreatment with proton pump inhibitors, vitamin D supplements and antibiotic prophylaxis against Pneumocystis jiroveci pneumonia when indicated. It is also important to ensure good control of blood pressure and blood glucose while on corticosteroids. On our AEACN survey (see online supplemental appendix 2 for details), the most popular bridging therapy was oral prednisone taper chosen by 38% of clinicians with 28% choosing to taper over months and 10% choosing to taper over days to weeks. This was followed by periodic IVIg (28%), rituximab alone or with oral prednisone (16%), and weekly or monthly IVMP (12%) including an approach of gradually increasing the intervals between infusions. Supplemental material SECTION 3: LONG-TERM MANAGEMENT OF AE Perhaps one of the most understudied aspects of AE is its long-term outpatient management following the initial attack. A major obstacle is identifying a clinician with expertise and interest in the long-term management of AE. Possible solutions include the integration of formal AE training in clinical neuroimmunology and MS fellowships or developing dedicated autoimmune neurology fellowships focusing on AE and related conditions (mirroring the limited autoimmune neurology programmes that are currently available in select institutions). Teleneurology and virtual visits may be another option to connect patients in remote areas to experts in academic centres. The long-term management of AE entails several equally important components as detailed later. Interpretation of NAA panel results Unlike acute management, the long-term management of AE is highly influenced by the presence and type of NAAs.27 In some cases, the results of the NAAs panel become available after the patient has been discharged although in patients with prolonged hospitalisation (eg, NMDAR-antibody encephalitis), the results become available while the patient is still hospitalised and can influence acute management. It is important to select a laboratory that uses the best available method for antibody detection. Cell-based-assay is the preferred method for neuronal surface antibodies while indirect tissue immunofluorescence and immunohistochemistry followed by Western blot confirmation is the standard for antibodies against intracellular antigens.25 Proper case selection for testing increases the likelihood of a positive test.28 Predicting scores such as the Antibody Prevalence in Epilepsy score (table 2) can help in case selection for NAAs testing factoring in the clinical presentation, cerebrospinal fluid (CSF) and MRI findings, and cancer history.28 A score greater than 3 predicts a high likelihood of identifying a neuronal specific antibody. Furthermore, it has been proposed that this scale could be used in the diagnostic criteria of AE in that a score greater than 3 with positive neuronal specific antibody is antibody positive AE and a score greater than 6 is probable AE. VIEW INLINE VIEW POPUP Table 2 Antibody prevalence in epilepsy and encephalopathy (APE2 score) When interpreting the NAAs panel, four possible results may be encountered. The first possibility is positivity for an antibody against intracellular antigens. These antibodies are highly specific and usually predictive of a paraneoplastic aetiology and a recognisable paraneoplastic syndrome in most cases especially those with typical clinical phenotype.29 A recent study evaluating the diagnostic yield of commercial onconeuronal antibodies in France found a low cancer predictability rate in a cohort of patients with frequent non-classical clinical presentations and questionable laboratory results (confirmed by another technique in only 30% of cases).30 The second possibility is positivity for one of the highly clinically relevant antibodies against neuronal surface antigens such as NMDAR or LGI1-antibodies. These antibodies are highly specific with reasonable positive predictive value for neurological autoimmunity and are known to be clinically relevant when present in the proper clinical setting.27 They can be associated with idiopathic or paraneoplastic forms of AE. Paraneoplastic cases are most frequently associated with NMDAR, AMPAR and GABA/BR antibodies.25 27 The third possibility is positivity for an antibody against neuronal surface antigens with limited clinical relevance such as VGCC, non-LGI1 non-CASPR2 ‘double negative’ VGKC and ganglionic AChR antibodies (table 1, part-1). These antibodies may or may not be relevant to the patient’s presentation depending on the clinical picture, and their presence should not preclude thorough exclusion of other potential causes of the neurological presentation.31–33 The antibody level (for some antibodies like GAD65-antibody), clinical presentation, disease course, CSF findings and smoking or cancer history are factors that can be used to determine the clinical relevance of the positive antibody.33–35 The NAAs confidence scale is one suggested tool to increase the confidence in the clinical relevance of these less specific antibodies (table 3).33 VIEW INLINE VIEW POPUP Table 3 Neuronal Autoantibody Confidence Scale* This scale has a 77% sensitivity, 94% specificity, 87% positive predictive value and 89% negative predictive value for clinical relevance of the positive NAAs. If the score is greater than 1, it is likely that the antibody is clinically relevant. Conversely, if the score is less than 1, it is likely that the antibody is clinically irrelevant, whereas a score of 1 is not predictive. If an alternative diagnosis was found during workup (eg, neurosarcoidosis, nutritional deficiency) then the positivity of one of these less specific antibodies should be considered a clinically irrelevant result not necessitating repeat cancer screening or addition or change of immunotherapy.33 34 It is to be noted that the clinical relevance of some of these antibodies is higher for peripheral neurological disorders as in the case of VGCC antibody with Lambert-Eaton myasthenic syndrome, and ganglionic AChR antibody with autoimmune autonomic ganglionopathy. Therefore, it is important to always correlate the clinical presentation to the positive antibody and question the clinical relevance of the test result if there is clinical-serological discordance. More recent NAAs panels emphasise the importance of clinical correlation and are based on clinical presentation (movement disorders vs epilepsy vs encephalopathy, etc) as opposed to aetiology (paraneoplastic vs idiopathic). As our knowledge and understanding of autoimmune neurology expands, antibodies with limited clinical relevance are expected to become obsolete or limited to specific panels. The fourth possibility is negativity for all commercially available antibodies. In that situation, it is important to determine whether the patient meets criteria for definite autoimmune limbic encephalitis or probable seronegative AE (online supplemental boxes 1 and 2).27 Patients with probable or definite seronegative AE should be tested for novel antibodies in research neuroimmunology laboratories if access to one is available (examples include Mayo Clinic, Pennsylvania, Oxford, Erasmus and Barcelona universities). If a patient was treated empirically for possible AE in the acute setting but tested negative for NAAs and did not meet criteria for definite or probable seronegative AE, it is very important that the diagnosis is challenged and workup for other potential diagnoses is initiated or repeated, especially if the response to immunotherapy was limited (figure 1). Supplemental material Supplemental material Figure 1 Interpretation of the neuronal autoantibody panel. *Anti-Hu (ANNA-1), anti-Ri (ANNA-2), ANNA-3, anti-SOX1 (AGNA), anti-amphiphysin, anti-CRMP-5 (anti-CV2), anti-Yo (PCA-1), PCA-2, high-titre anti-GAD65. **Anti-NMDA-R, anti-LGI1, anti-CASPR2, anti-AMPA-R, anti-GABA-A/B, PCA-Tr, anti-DPPX, anti-mGluR1, anti-mGluR2, anti-mGluR5, anti-IgLON5, anti-AQP4, anti-MOG. ***Non-LGI1 non-CASPR2 anti-VGKC, anti-P/Q VGCC, anti-N VGCC, Ach-b, Ach-M, Ach-G, Striational. Low-titre anti-GAD65 is an antibody against cytoplasmic antigen but is of questionable clinical significance. Adapted with permission from George et al.40 Determining the need for long-term immunosuppression As mentioned previously, it is important to initiate bridging immunosuppression after acute therapy in the hospital followed by a gradual taper. The more difficult task is selecting patients for long-term immunosuppression. The recurrence rate is highest in conditions associated with clinically relevant neuronal surface antibodies and much lower in conditions associated with antibodies against intracellular antigens, which tend to follow a relentless progressive course rather than a relapsing one but may remit after cancer treatment in some patients.25 27 Determining what constitutes a recurrence is itself a difficult task. Fluctuation of cognition, breakthrough seizures and other transient worsening of residual symptoms after the initial attack are common and do not necessarily represent a recurrence of the autoimmune inflammation. In some AE types, relapses tend to be phenotypically identical to the initial attack as in LGI1-antbiody encephalitis36 or similar but milder in severity as in NMDAR-antibody encephalitis.36 In other AE subtypes, relapses can present differently from the initial attack, as is the case of CASPR2-antibody encephalitis.37 In all cases, getting supportive objective information from MRI, EEG and/or CSF can help confirm a true relapse. Recurrence rates in AE associated with neuronal surface antibodies range from 10% to 35% based on retrospective observational studies but these rates are confounded by short follow-up periods in most of the reported case series and review articles.13 22 24 38 On the other hand, suspecting AE and testing the antibody panel may sometimes happen only after a relapse of encephalopathy so the true rates of monophasic disease may also be underestimated.38 The recurrence rate is unknown in seronegative AE. With this uncertainty and the low recurrence rates in seropositive cases, it is difficult to justify prolonged immunosuppression though in some cases a few to several years of maintenance immunosuppression may be indicated. Decisions regarding long-term immunosuppression should take in consideration published relapse rates for each specific clinical syndrome as well as severity of the initial attack and individual risks related to immunosuppression. Relapse rates and the value of long-term immunosuppression are among the key areas in need for further future research. In the meantime, any decision regarding maintenance immunosuppression in patients with AE should carefully weigh the risks versus potential benefits and incorporate evolving data about relapse risk for each specific clinical syndrome. Patients who experience a definite clinical relapse based on high clinical suspicion and supported by objective evidence of ancillary tests (eg, MRI or EEG) should start long-term immunosuppression after relapse treatment.23 Although azathioprine and mycophenolate mofetil (MMF) have been used in this setting, the use of rituximab may have the added benefit of a potentially faster onset of action (second-line acute therapy) and less carcinogenic potential with prolonged use compared with other agents.23 24 Rituximab can be used as both a second-line agent for acute immunosuppression and as a long-term immunosuppressant for recurrent cases. Rituximab, however, does not deplete the antibody-secreting cells which are typically CD20-negative. In these conditions, rituximab may work by deleting the antigen-specific memory B-cell populations and hence preventing the formation of new plasmablasts which secrete the pathogenic antibodies.17 The use of other B-cell therapies (eg, humanised anti-CD20 and anti-CD19 monoclonal antibodies) may be worth exploring in future research. Overlapping with oral corticosteroids is needed for 3–6 months when using azathioprine or MMF due to their delayed onset of action. On our AEACN survey, in response to a question in the check-all-that-apply format, 70% of responders indicated they would start long-term immunosuppression in AE associated with antibodies against neuronal surface antigens after a second attack while 50% indicated they would start after the first attack. As for seronegative AE, 61% indicated they would start long-term immunosuppression after a second attack and only 10.4% indicated they would start after the first attack. However, these generalised survey results should be treated with caution since clinicians’ practice is influenced by the specific AE subtype they see most frequently. In addition, many clinical specifics influence the decision regarding long-term immunosuppression as mentioned earlier. For patients with antibodies against intracellular antigens in whom the associated tumour has been treated, shorter bridging therapy may be considered. This is because recurrence rates are low after tumour treatment and since the response to immunotherapy is generally limited in those patients.23 24 29 In patients with antibodies against intracellular antigens in whom no tumour was found, a shorter course of bridging therapy is also advisable especially if they have not had a robust response to acute immunotherapy since prolonged immunosuppression may increase the risk of progression of the presumed underlying tumour. Long-term immunosuppression should generally be used with caution in those patients for the same reasons. This concept was reflected in the AEACN survey results as only 29% of responders indicated they would start long-term immunosuppression after treatment of the coexisting tumour for AE associated with antibodies against intracellular antigens and only 46% indicated they would start long-term immunosuppression if a tumour was not found. Patients with ongoing progression of neurological disability may be selected for immunosuppression with careful and frequent cancer screening. On the AEACN survey, the most popular choice for long-term immunosuppression for relapsing AE was rituximab chosen by 46% of responders, followed by azathioprine (15%), MMF (12%), maintenance corticosteroids (6%) and maintenance IVIg (4%). Some clinicians (12%) indicated that their choice of the long-term immunosuppressive agent depends on the antibody type with rituximab being preferred for antibodies against neuronal surface antigens (humoral autoimmunity) and other agents such as azathioprine or MMF preferred for antibodies against intracellular antigens and for seronegative AE (for presumed cellular autoimmunity). Some responders stressed the importance of patients’ comorbidities and preferences in making this decision. The optimal duration of maintenance therapy in relapsing forms of AE is unknown but published empiric approaches suggest initial maintenance period of 3 years followed by re-evaluation and attempt at withdrawal of immunosuppression.22–25 This suggested duration of long-term immunotherapy is arbitrary and not evidence-based. Retrospective studies in NMDAR-antibody encephalitis showed a small rate of recurrence within a 2-year duration but patients who received second-line immunotherapy (predominantly rituximab) had lower recurrence rates.22 Patients who have more than one relapse while on immunosuppression or while being weaned should be considered for extended immunosuppression.23 On the AEACN survey, the most popular choice for the duration of long-term immunosuppression in relapsing AE was 3 years selected by 44% of responders followed by 2 years (19%), 1 year (13%), lifelong (7%) and 6 months (3%). Of note, 13% of survey responders indicated that the duration of immunosuppression would depend on multiple factors including severity of prior attacks, tolerability of the immunosuppressive agents, antibody type and patient’s comorbidities and cancer risk. The best long-term preventive therapy for relapsing AE depends on the specific immunopathology of each AE subtype. The current empiric approaches are expected to improve as the specific pathogenic mechanism of each serological and/or clinical AE subtype is refined. A tailored approach with more selective immunomodulation to each specific syndrome will likely improve outcomes and limit unnecessary side effects. The value of non-cell-depleting immunotherapies (eg, complement or cytokine inhibitors) is yet to be fully explored in the long-term management of AE. The use of interleukein-6 inhibitors as second-line rescue therapy has already been discussed in part-1 but their use as maintenance therapy for recurrent AE is yet to be evaluated. The rarity of individual AE subtypes hinder large-scale clinical trials but this can possibly be overcome through international multicentre collaborations similar to the recent NMOSD trials. Consolidation of AE subtypes with similar pathogenic mechanisms could be considered to facilitate recruitment and expedite the advancement of evidence-based medicine in AE. Determining the need for and frequency of periodic cancer screening Initial cancer screening should be considered for most adult patients with AE at the time of presentation and at the time of any definite relapse.39 In patients in whom a tumour was found and treated, recommendations for periodic screening are dictated by established guidelines for each cancer type. In patients in whom a tumour is not found initially, periodic tumour screening every 6–12 months for an average of 4 years should be considered for patients with antibodies against intracellular antigens given their strong association with tumours.39 As for antibodies against neuronal surface antigens, tumour association is less frequent and is variable from one antibody to another. There is currently no clear guidelines for the optimal frequency and duration for cancer screening in adult patients with AE with antibodies against neuronal surface antigens, which can understandably vary depending on the specific antibody. The importance of early tumour detection should be weighed against the risks of frequent and prolonged cancer screening including increased cost and the potential for incidental findings and subsequent unnecessary investigations or interventions. On our AEACN survey (figure 2), the majority of responders (49%) opted to cancer screening for 4 years in those patients with half the responders choosing semiannual screening and half choosing annual screening during that period. Screening yearly for 2 years was chosen by 18% of responders while only 6% indicated that no periodic cancer screen is necessary after the initial screen. Some clinicians (18%) indicated that the frequency and duration of cancer screening must be tailored according to published rates of cancer association for each specific antibody. However, it should also be noted that many patients with these conditions would never have a tumour discovered. Figure 2 Autoimmune Encephalitis Alliance Clinicians Network survey results for periodic cancer screening. AE, autoimmune encephalitis. *Excluding immune checkpoint inhibitors. The value of periodic cancer screening in patients with seronegative AE is unknown but should be considered in patients with relapsing disease and those with definite limbic encephalitis in whom the connection to cancer is expected to be higher than other neuroanatomical variants.29 39 On the AEACN survey, 46% of responders indicated they would perform cancer screening every 6–12 months for 4 years in patients with seronegative limbic encephalitis while 20% chose yearly screening for 2 years and 21% indicated that no periodic cancer screening is necessary after the initial screen. As for other seronegative neuroanatomical variants (eg, cortical, brainstem), fewer clinicians felt the need to screen patients for 4 years (36%) than in the case of limbic encephalitis and relatively more clinicians chose screening for 2 years (24%) or no screening (24%). Some clinicians (10%) indicated that the frequency and duration of cancer screening in seronegative AE would depend on each patient’s demographics and social habits (eg, age, smoking, etc). In patients with AE in the setting of ICI cancer treatment, cancer monitoring will be dictated by the oncologist according to established guidelines for each cancer type. When AE occurs in the setting of other immunomodulating therapies (eg, TNF-alpha inhibitors, daclizumab) or other well-known triggers (eg, post-herpetic), periodic cancer screening may not be as imperative since a paraneoplastic aetiology is less likely in the presence of an established trigger. On our AEACN survey, this concept was reflected in the answers addressing cancer screening following post-herpetic AE as 65% of responders indicated that there is no need for periodic screening following the initial screen. However, in iatrogenic AE in the setting of immumodulating therapies other than ICIs, only 39.3% of responders opted not to perform periodic cancer screening after the initial one indicating less confidence in the aetiological relationship between these agents and AE development especially in patients with cancer risk factors. Nevertheless, most clinicians selected less stringent cancer screening protocols in patients with iatrogenic AE (only 25% recommended cancer screening for a duration of 4 years). Whole body FDG-PET is a single test that may be used for periodic screening in addition to recommended age appropriate screening tests (eg, mammograms, colonoscopy).39 An initial first-line screening study (eg, CT) may be required prior to approval of FDG-PET, although approval policies vary by insurer. FDG-PET can detect tumours that are missed by CT making it a higher yield test in paraneoplastic conditions since associated tumours are usually in early development.39 Medical insurance providers should allow FDG-PET coverage in patients with paraneoplastic syndromes and/or positive NAAs as discussed in part-1. FDG-PET is not ideal for seminoma/teratoma detection so periodic pelvic/scrotal ultrasound should be considered in case of AE serological or phenotypical subtypes suggestive of these tumours (eg, anti-NMDR or anti-Ma2 encephalitis or their phenotypes). A more targeted periodic cancer screening can also be considered for certain antibodies with specific cancer associations (eg, pelvic ultrasound and mammogram/breast MRI for anti-Yo antibody). Physical and neuropsychological rehabilitation Patients with ataxia, spasticity and other mobility issues may benefit from physical therapy and neurorehabilitation. More importantly, patients with short-term memory impairment and other cognitive deficits should undergo neuropsychological evaluation to identify those in need for neuropsychological rehabilitation programmes. The value of cognitive and neuropsychological rehabilitation in AE has not been investigated in a systematic manner but clinical experience supports a pivotal role in recovery after the acute phase. Response to neuropsychological rehabilitation may vary according to patient’s age, comorbidities and extent/location of permanent brain damage if any. It is unknown if antibody type influences responsiveness to neuropsychological rehabilitation. Studies on cognitive outcomes of AE and the role of neuropsychological rehabilitation is among the most pressing needs in AE research. Some patients may require modification of their house or workplace. Many patients may need formal functional capacity evaluations to determine their ability to go back to the workforce, and most will need aggressive management of vascular risk factors and promotion of healthy lifestyle to avoid further cognitive decline. DISCUSSION AND SUMMARY In this two-part project, we analysed each step in AE management in a real-life chronological order that covers the first neurological presentation, diagnostic workup, acute management, bridging therapy, and long-term management and monitoring. We focused on practical management questions and used published research and expert opinion to provide broad recommendations to clinicians. We understand that AE is a heterogeneous disease and that treatment strategies may differ from one antibody-related syndrome and/or one clinical subtype to another. However, individual AE syndromes are rare and information on the specific antibody is usually lacking at the time of presentation. This makes it necessary to establish a common general approach to AE to guide initial management until the specific antibody is revealed. Moreover, many cases of AE are not linked to any of the commercially available antibodies, which adds to the importance of having a common approach. In addition, many AE syndromes have common clinical and pathogenic features making standardisation of certain aspects of both acute and long-term management possible for some of these syndromes. A major limitation to our survey questionnaire is generalisation. When addressing a diverse clinical entity like AE with a wide spectrum of clinical phenotypes and patient demographics/comorbidities, it is difficult to develop specific questions for every possible clinical scenario. Therefore, our recommendations may not be suitable for all patients and clinicians will still need to make individual decisions based on each patient’s unique circumstances. Our AEACN survey results highlight the diversity of practice across institutions when it comes to AE management and emphasise the need for development of standards of care. Although no consensus was reached for most of the survey questions, the survey results showed which approaches are most popular among AE clinicians and which steps in AE management are most divisive and therefore require more research. More formal consensus techniques like the Delphi method were not implemented to avoid misinterpretation of our recommendations as firm treatment guidelines. A major goal of this paper was to showcase both agreements and disagreements in AE management in order to inform future observational and interventional studies. In this evolving field, presenting firm consensus guidelines in the absence of strong scientific evidence can have a negative impact on future research efforts. On the other hand, translating practice patterns into management recommendations remains a major limitation to this paper. However, the recommendations did not rely solely on survey results and incorporated available evidence from several AE subtypes and related immune-mediated disorders. The inclusion of multiple subspecialties and several countries in the survey enriched the results and made our recommendations applicable to a larger audience. However, this diversity in specialty and geographical locations inevitably introduced a degree of responder bias given the difference in practice per specialty (eg, paediatric vs adult neurologists) and location (eg, some therapeutic and diagnostic interventions are not readily available in some countries/institutions). Our recommendations are meant to serve as a general guidance for clinicians until better quality evidence becomes available for each AE subtype and are expected to evolve over time as more data emerge in the future. A summary of the recommendations for acute management was presented after part-1. Box 1 includes a summary of the recommendations for long-term management. Box 1 Best practice recommendations summary for long-term management of autoimmune encephalitis Positive antibody against intracellular antigen (classical onconeuronal antigens) and typical clinical picture: refer to oncology for treatment and surveillance of tumour if one was found. If no tumour was found, initiate semiannual to annual cancer screening for at least 4 years. Treat neurological relapses with intravenous methyl-prednisolone and/or cyclophosphamide as necessary but avoid long-term immunosuppression. Positive antibody against neuronal surface antigen with high clinical relevance and typical clinical picture: consider periodic tumour screening based on the type of antibody and each patient’s cancer risk factors. Some neuronal surface antibodies with higher rates of tumour association may require more frequent screening as in gamma-Aminobutyric acid-B receptor (GABABR)-antibody encephalitis and some may require less frequent screening as in leucine-rich glioma inactivated-1-antibody encephalitis. Consider initiating at least annual cancer screening for an average of 2–4 years based on antibody type. A more selective screening approach could be considered for antibodies with specific tumour associations. Consider long-term immunosuppression preferably with rituximab (based on presumed antibody-mediated immunity and on N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis studies) after a second attack. May consider starting long-term immunosuppression after the first attack in patients with severe initial presentation or risk factors for relapse (eg, persistently positive oligoclonal bands). Overlap with short-term oral corticosteroids after initiation of long-term agent. The duration of long-term immunosuppression depends on relapse rate, relapse severity and tolerability of the immunosuppressive agent. Positive antibody against neuronal surface antigen with low clinical relevance to the clinical presentation: evaluate confidence in the clinical relevance of the positive antibody based on clinical and ancillary data. Evaluate for alternative aetiologies. If the diagnosis of autoimmune encephalitis (AE) is felt to be probable and no other aetiology found then follow recommendation 2. Seronegative AE: confirm the diagnosis according to published criteria and exclude alternative causes. May consider initiating annual cancer screening for an average of 4 years for seronegative definite autoimmune limbic encephalitis and may consider periodic screening for an average of 2 years for all other neuroanatomical variants. Start long-term immunosuppression with rituximab, mycophenolate mofetil or azathioprine after a second attack. Overlap with short-term corticosteroids after initiation of long-term agent. The duration of long-term immunosuppression depends on relapse rate, relapse severity and tolerability of the immunosuppressive agent. Recommendations for seronegative AE are particularly anecdotal and more research is needed for this subtype of AE. For all AE subtypes: treat residual symptoms including seizures, movement disorders, psychiatric symptoms, spasticity, sleep dysfunction and dysautonomia. Also start de-escalation of symptomatic medications when appropriate. Start physical, occupational and speech therapy depending on residual deficits. Strongly consider neuropsychological rehabilitation although the value behind this intervention is in need for further research to establish scientific evidence.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Presentation, Diagnosis, and Management | Pediatric Annals

1.Hacohen Y, Banwell B. Treatment Approaches for MOG-Ab-associated demyelination in children. Curr Treat Options Neurol. 2019; 21(1):2. 10.1007/s11940-019-0541-x PMID:30671648 Google Scholar 2.Reindl M, Waters P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol. 2019; 15(2):89–102. 10.1038/s41582-018-0112-x PMID:30559466 Google Scholar 3.de Mol CL, Wong Y, van Pelt EDet al.. The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults. Mult Scler. 2020; 26(7):806–814. 10.1177/1352458519845112 PMID:31094288 Google Scholar 4.Bruijstens AL, Lechner C, Flet-Berliac L, et al.E.U. paediatric MOG consortium. E.U. paediatric MOG consortium consensus: Part 1 - classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders. Eur J Paediatr Neurol. 2020; 29:2–13. 10.1016/j.ejpn.2020.10.006 PMID:33162302 Google Scholar 5.Mao L, Yang L, Kessi Met al.. Myelin oligodendrocyte glycoprotein (MOG) antibody diseases in children in Central South China: clinical features, treatments, influencing factors, and outcomes. Front Neurol. 2019; 10:868. 10.3389/fneur.2019.00868 PMID:31440204 Google Scholar 6.Jurynczyk M, Messina S, Woodhall MRet al.. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017; 140(12):3128–3138. 10.1093/brain/awx276 PMID:29136091 Google Scholar 7.Sato DK, Callegaro D, Lana-Peixoto MAet al.. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014; 82(6):474–481. 10.1212/WNL.0000000000000101 PMID:24415568 Google Scholar 8.Hacohen Y, Wong YY, Lechner Cet al.. Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. JAMA Neurol. 2018; 75(4):478–487. 10.1001/jamaneurol.2017.4601 PMID:29305608 Google Scholar 9.Flanagan E. Neuromyelitis optica spectrum disorder and other non-multiple sclerosis central nervous system inflammatory diseases. Continuum. 2019; 25(3)815–844. 10.1212/CON.0000000000000742 Google Scholar 10.Chitnis T. Pediatric central nervous system demyelinating diseases. Continuum. 2019; 25(3)793–814. 10.1212/CON.0000000000000730 PMID:31162317 Google Scholar 11.Hacohen Y, Rossor T, Mankad Ket al.. ‘Leukodystrophy-like’ phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease. Dev Med Child Neurol. 2018; 60(4):417–423. 10.1111/dmcn.13649 PMID:29288492 Google Scholar 12.Wegener-Panzer A, Cleaveland R, Wendel EMet al.. Clinical and imaging features of children with autoimmune encephalitis and MOG antibodies. Neurol Neuroimmunol Neuroinflamm. 2020; 7(4):e731. 10.1212/NXI.0000000000000731 PMID:32358225 Google Scholar 13.Cellucci T, Van Mater H, Graus Fet al.. Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient. Neurol Neuroimmunol Neuroinflamm. 2020; 7(2):e663. 10.1212/NXI.0000000000000663 PMID:31953309 Google Scholar 14.Armangue T, Olivé-Cirera G, Martínez-Hernandez Eet al.Spanish Pediatric anti-MOG Study Group. Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study. Lancet Neurol. 2020; 19(3):234–246. 10.1016/S1474-4422(19)30488-0 PMID:32057303 Google Scholar 15.Armangue T, Capobianco M, de Chalus A, et al.E. U. paediatric MOG consortium. E.U. paediatric MOG consortium consensus: part 3 - biomarkers of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders. Eur J Paediatr Neurol. 2020; 29:22–31. 10.1016/j.ejpn.2020.11.001 PMID:33191096 Google Scholar 16.Lee SK, Lee ST. The laboratory diagnosis of autoimmune encephalitis. J Epilepsy Res. 2016; 6(2):45–50. 10.14581/jer.16010 PMID:28101474 Google Scholar 17.Bruijstens AL, Wendel EM, Lechner Cet al.. E.U. paediatric MOG consortium consensus: part 5 - treatment of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders. Eur J Paediatr Neurol. 2020; 29:41–53. 10.1016/j.ejpn.2020.10.005 PMID:33176999 Google Scholar 18.Ramanathan S, Mohammad S, Tantsis Eet al.Australasian and New Zealand MOG Study Group. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry. 2018; 89(2):127–137. 10.1136/jnnp-2017-316880 PMID:29142145 Google Scholar 19.Papp KA, Haraoui B, Kumar Det al.. Vaccination guidelines for patients with immune-mediated disorders on immunosuppressive therapies. J Cutan Med Surg. 2019; 23(1):50–74. 10.1177/1203475418811335 PMID:30463418 Google Scholar 20.Heijstek MW, Ott de Bruin LM, Bijl Met al.EULAR. EULAR recommendations for vaccination in paediatric patients with rheumatic diseases. Ann Rheum Dis. 2011; 70(10):1704–1712. 10.1136/ard.2011.150193 PMID:21813547 Google Scholar 21.Bruijstens AL, Breu M, Wendel EM, et al; EU. paediatric MOG consortium.E.U. paediatric MOG consortium consensus: part 4 - outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders. Eur J Paediatr Neurol. 2020; 29:32–40. 10.1016/j.ejpn.2020.10.007 PMID:33183945 Google Scholar 22.Pohl D, Alper G, Van Haren Ket al.. Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome. Neurology. 2016; 87(9)(suppl 2):S38–S45. 10.1212/WNL.0000000000002825 PMID:27572859 Google Scholar 23.Dutra BR.et al.. Neuromyelitis optica spectrum disorders: spectrum of MR imaging findings and their differential diagnosis. Neurol/Head Neck Imag. 2018; 38(1). 10.1148/rg.2018170141 Google Scholar 24.Yeh EA, Graves JS, Benson LA, Wassmer E, Waldman A. Pediatric optic neuritis. Neurology. 2016; 87(9)(suppl 2):S53–S58. 10.1212/WNL.0000000000002822 PMID:27572862 Google Scholar 25.Absoud M, Greenberg BM, Lim M, Lotze T, Thomas T, Deiva K. Pediatric transverse myelitis. Neurology. 2016; 87(9)(suppl 2):S46–S52. 10.1212/WNL.0000000000002820 PMID:27572861 Google Scholar
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Postdoctoral Fellows in Neuroinflammatory Disease and Neuroscience |

Postdoctoral Fellows in Neuroinflammatory Disease and Neuroscience, with University of California San Francisco (UCSF). Apply Today.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Diagnostic Imaging in Autoimmune Encephalitis - Dr. Michael Fagien | Building Bridges 2021

No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

MyJournals.org - Science - 'Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report' (BMC Psychiatry)

MyJournals.org - Science - 'Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report' (BMC Psychiatry)...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Clinical Profile and Treatment Response in Patients with CASPR2 Antibody-Associated Neurological Disease

Clinical Profile and Treatment Response in Patients with CASPR2 Antibody-Associated Neurological Disease | AntiNMDA | Scoop.it
The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited.We report the clinical profile and emphasize response ...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis | Neurology

Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis | Neurology | AntiNMDA | Scoop.it
SHARE July 06, 2021; 97 (1) RESEARCH ARTICLE Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis View ORCID ProfileMar Guasp, Eloi Giné-Servén, Estibaliz Maudes, View ORCID ProfileMireia Rosa-Justicia, Eugenia Martínez-Hernández, Ester Boix-Quintana, Miquel Bioque, Virginia Casado, Yasmina Módena-Ouarzi, Nicolau Guanyabens, Desiree Muriana, Gisela Sugranyes, Isabella Pacchiarotti, Eva Davi-Loscos, Cristina Torres-Rivas, View ORCID ProfileJosé Ríos, Lidia Sabater, Albert Saiz, Francesc Graus, Josefina Castro-Fornieles, Eduard Parellada, View ORCID ProfileJosep Dalmau First published May 12, 2021, DOI: https://doi.org/10.1212/WNL.0000000000012191 FULL PDF SHORT FORM CITATION PERMISSIONS MAKE COMMENT SEE COMMENTS Downloads110 Article Figures & Data Info & Disclosures CME Course 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. Abstract Objectives To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP). Methods This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed. Results One hundred five patients were included; their median age was 30 (range 14–75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features). Conclusions NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided. Glossary AP=autoimmune psychosis; CBA=cell-based assay; CI=confidence interval; DSM=Diagnostic and Statistical Manual of Mental Disorders; FEP=first episode psychosis; IgG=immunoglobulin G; IQR=interquartile range; NMDAR=NMDA receptor; NMDAR-abs=NMDAR antibodies; WBC=white blood cells Footnotes Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. Editorial, page 16 CME Course: NPub.org/cmelist Podcast: NPub.org/ogxa6o Received December 2, 2020. Accepted in final form March 26, 2021. © 2021 American Academy of Neurology View 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 MORE ONLINE CME Course RELATED ARTICLES TOPICS DISCUSSED ALERT ME
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Psychiatric Phenotypes of Pediatric Patients With Seropositive Autoimmune Encephalitis | American Academy of Pediatrics

Psychiatric Phenotypes of Pediatric Patients With Seropositive Autoimmune Encephalitis | American Academy of Pediatrics | AntiNMDA | Scoop.it
Abstract OBJECTIVES Patients with autoimmune encephalitis (AE) often present with symptoms that are broadly characterized as psychiatric or behavioral, yet little attention is given to the precise symptomatology observed. We sought to more fully define the psychiatric symptoms observed in patients with anti–N-methyl-D-aspartate receptor (NMDAR), anti–glutamic-acid-decarboxylase 65 (GAD65), and anti–voltage-gated-potassium-channel complex (VGKC) antibody-mediated AE using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition nomenclature. METHODS We present a case series (n = 25) using a retrospective chart review of 225 patients evaluated for AE in a tertiary care academic medical center between 2014 and 2018. The included patients were ≤18 years old with anti-NMDAR AE (n = 13), anti-GAD65 AE (n = 7), or anti-VGKC AE (n = 5). The frequency of neuropsychiatric symptoms present at the onset of illness and time to diagnosis were compared across groups. RESULTS Psychiatric symptoms were seen in 92% of patients in our cohort. Depressive features (72%), personality change (64%), psychosis (48%), and catatonia (32%) were the most common psychiatric symptoms exhibited. On average, patients experienced impairment in ≥4 of 7 symptom domains. No patients had isolated psychiatric symptoms. The average times to diagnosis were 1.7, 15.5, and 12.4 months for anti-NMDAR AE, anti-GAD65 AE, and anti-VGKC AE, respectively (P < .001). CONCLUSIONS The psychiatric phenotype of AE in children is highly heterogenous. Involving psychiatry consultation services can be helpful in differentiating features of psychosis and catatonia, which may otherwise be misidentified. Patients presenting with psychiatric symptoms along with impairments in other domains should prompt a workup for AE, including testing for all known antineuronal antibodies. Copyright © 2021 by the American Academy of Pediatrics
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management | Journal of Neurology, Neurosurgery & Psychiatry

Introduction Autoimmune encephalitis (AE) comprises a group of non-infectious immune-mediated inflammatory disorders of the brain parenchyma often involving the cortical or deep grey matter with or without involvement of the white matter, meninges or the spinal cord.1–4 The original description of AE was based on paraneoplastic conditions related to antibodies against intracellular onconeuronal antigens such asANNA-1/anti-Hu.5 6 These ‘classical’ antibodies are non-pathogenic but represent markers of T-cell-mediated immunity against the neoplasm with secondary response against the nervous system. In recent years, an increasing number of antibodies targeting neuronal surface or synaptic antigens have been recognised such as N-MethylD-Aspartate Receptor (NMDAR)-antibody and Leucine-richglioma inactivated (LGI1)-antibody.1 Most of these surface antibodies have been shown to be likely pathogenic and are thought to mediate more immunotherapy-responsive forms of AE and have less association with tumours. Specific types of encephalitis can occur in the setting of antibodies against oligodendrocytes (eg, anti-myelin oligodendrocyte glycoprotein (MOG) brainstem encephalitis) or astrocytes (eg, anti-aquaporin-4 (AQP4) diencephalic encephalitis, anti-glial fibrillary acidic protein (GFAP) meningoencephalitis). In addition, some AE patients do not have any identifiable antibodies (seronegative) representing a disease category with novel, yet to be identified antibodies or T-cell mediated disease. Online supplemental appendix S1 contains a list of the commercially available neuronal autoantibodies (NAAs). Supplemental material Recent epidemiological studies suggest that AE is possibly as common as infectious encephalitis with an estimated prevalence rate of 13.7/100 000.7 The rapidly advancing knowledge of new antibodies and their associated syndromes has created a new and growing field of autoimmune neurology.8 However, advances from the laboratory bench have not been paralleled by advancement in clinical practice, leading to a large knowledge gap and many unanswered questions regarding the acute and long-term management of AE. The heterogeneity of AE presentation and findings on ancillary testing hinder large-scale clinical trials and limit the quality of evidence behind AE management. The objective of this paper is to evaluate available evidence for each step in AE management and provide expert opinion when evidence is lacking. Although the turnaround time of commercial NAAs panels may improve in the near future, currently these results are often unavailable at the time of early evaluation and management. Moreover, current commercial NAAs panels are inherently limited in their ability to diagnose AE, given the ever-growing numbers of antibodies identified and the likelihood of T-cell mediated pathogenesis in some cases. Consequently, clinicians have to approach AE initially as a clinical entity when deciding on investigations and treatment.1 Long-term management can then be modified according to the type of antibody identified, if any. Therefore, the aim of this paper is to emphasise the practical acute and long-term management of AE as a broad category rather than focusing on individual antibody syndromes. Another important goal is to represent the practice of experienced clinicians from different clinical and geographical backgrounds. Methods Core authors from the Autoimmune Encephalitis Alliance Clinicians Network (AEACN) developed the first draft of this paper (HA, JCP, SI, RCD, EPF, PG, AJ, YL, AR-G, IR, SJP and MJT). The AEACN is comprised of self-identified clinicians with interest and clinical expertise in AE management listed by the AE Alliance, a non-profit organisation founded by AE patients and families to establish a supportive community for patients and caregivers, enhance clinical collaboration, and facilitate AE scientific research. The AEACN includes a multidisciplinary international group of adult and paediatric neurologists, rheumatologists, psychiatrists, neuropsychologists and other specialists with real-life experience in AE management. The authors of the first draft reviewed available literature to compile existing evidence for every step in AE management. Where evidence was lacking or controversial, an electronic survey was distributed to all AEACN members to solicit individual responses. The survey questions were strategically planned to look at initial treatment, continued care and finally long-term management. After adding survey results to the manuscript, the updated version was circulated to all participating AEACN members for edits and further suggestions. Survey results The survey was distributed to 147 Clinical members. Sixty-eight (46%) members responded including the core authors. The most represented specialty/subspecialty of the respondents was neuroimmunology (66%), followed by general neurology (21%), paediatric neurology (16%), epilepsy (9%), behavioural/cognitive neurology (6%), hospital neurology-neurohospitalist (6%), neuromuscular neurology (6%), paediatric rheumatology (6%), neurocritical care (4%), psychiatry (4%), movement disorders (3%), general paediatrics (3%) and one specialist (1.5%) each of the following: autonomic disorders, adult rheumatology and paediatric critical care. Twenty-five members (37%) indicated more than one subspecialty. Clinicians from 17 countries participated including USA (69%), Brazil (4%), Canada (3%), China (3%), Spain (3%), Argentina, Australia, Indonesia, Israel, Italy, the Netherlands, the Philippines, Singapore, South Korea, Switzerland, Turkey and the UK (countries listed in a descending order based on the number of responders and alphabetically when the number of responders was equal). Of the total participating members, 88% practiced at academic tertiary referral centres and 76% were active in AE clinical research or scholarly publications. The participating members indicated personal clinical experience with an average of 7.3 AE subtypes (range 1–13 subtypes, median 8 subtypes). In total, 9% of the participating members were affiliated with reference neuroimmunology laboratories with NAAs testing capabilities. The results of individual survey questions are presented under the corresponding sections of AE management. The final draft was approved by all participating AEACN members after four rounds of revisions. The paper aimed to answer prespecified clinical questions as detailed below. Data availability statement The results of the survey are partially summarised in figure 1 and the detailed responses of all survey questions are published as online supplemental document 2. Supplemental material Figure 1 AEACN survey results for acute and bridging therapy. AE, autoimmune encephalitis; AEACN, Autoimmune Encephalitis Alliance Clinicians Network; IVMP, intravenous methylprednisolone; IVIg, intravenous Ig; PLEX, plasma exchange. Section 1: diagnosis of AE When to suspect AE clinically? A detailed history and examination is the first and most important step in AE diagnosis. The immune reaction in AE often results in acute or subacute presentation of a duration less than 3 months.1 Chronic presentations are only seen in some of these conditions, especially LGI1, Contactin-associatedprotein-like 2 (CASPR2), Dipeptidyl-peptidase-likeprotein 6 (DPPX) and Glutamicacid decarboxylase 65 (GAD65)-antibody encephalitis, and should otherwise raise suspicion of a neurodegenerative disease or other etiologies.9 Likewise, hyperacute presentations are also atypical and a vascular aetiology should be considered in those cases. A recurrent course may point towards an autoimmune aetiology but unlike the typical relapsing-remitting course of multiple sclerosis and systemic inflammatory disorders, AE relapses are rare and often result from insufficient treatment or rapid interruption of immunotherapy. A monophasic course is more common in idiopathic AE while a progressive course may be seen in some paraneoplastic syndromes especially paraneoplastic cerebellar degeneration, which tends to plateau after the cancer is treated. Patients with known cancer or those at increased cancer risk (smokers, the elderly, and patients with rapid unintentional weight loss) are prone to paraneoplastic AE, while patients with personal or family history of other autoimmune disorders are at increased risk of idiopathic AE.10 A preceding viral infection, fever or viral-like prodrome is common.11 AE may be triggered by herpes simplex virus (HSV) encephalitis or certain immune-modulating therapies such as TNFα inhibitors, and immune-checkpoint inhibitors (ICIs)—the latter can cause an accelerated form of paraneoplastic encephalitis in patients with advanced cancer.1 12 Table 1 shows practical classification concepts in AE. VIEW INLINE VIEW POPUP Table 1 Proposed classification concepts in autoimmune encephalitis The immune reaction in AE is usually diffuse, resulting in multifocal brain inflammation and occasionally additional involvement of the meninges, spinal cord and/or the peripheral nervous system.3 6 This diffuse inflammation may or may not be detectable on ancillary testing but it usually results in a polysyndromic presentation which is a clinical hallmark of AE. Although some antibodies have been linked to stereotypical symptoms (eg, oromandibular dyskinesia, cognitive/behavioural changes, and speech and autonomic dysfunction in NMDAR-antibody encephalitis, faciobrachial dystonic seizures in LGI1-antibody encephalitis, etc), there is significant symptom overlap between all antibodies and all forms of AE.1 11 Symptoms vary according to the anatomical localisation of inflammation and there are several clinical-anatomical syndrome categories in AE as summarised in table 2. VIEW INLINE VIEW POPUP Table 2 Anatomical-clinical syndromes of autoimmune encephalitis What investigations should be ordered when AE is suspected? After AE is suspected clinically, a detailed workup is needed to confirm the diagnosis and exclude competing possibilities like infective encephalitis or systemic/metabolic causes. In most cases, the workup starts with brain imaging and cerebrospinal fluid (CSF) analysis. The diagnostic algorithm follows the structure summarised in figure 2 and detailed below: Aim 1: confirming the presence of focal or multifocal brain abnormality suggestive of encephalitis Figure 2 Diagnostic algorithm for autoimmune encephalitis. *EEG can confirm focal or multifocal brain abnormality and rule out subclinical seizures. **In addition to neuronal autoantibodies, cerebrospinal fluid should be tested for infections, inflammatory markers (IgG index and oligoclonal bands), and in some cases cytology. ***In addition to neuronal autoantibodies, the differential diagnosis generated based on MRI results will guide what blood tests to send. ****In most cases, general neoplasm screening starts with CT then other screening modalities are added until a neoplasm is found or eventually ruled out. If the clinical picture is highly suggestive of a specific neoplasm, a targeted screening approach could be implemented (eg, starting with pelvic ultrasound if the clinical picture is suggestive of anti-NMDAR encephalitis). AE, autoimmune encephalitis; EEG, electroencephalogram; MRI WWO, MRI with or without contrast; PET, positron emission tomography. Brain MRI In addition to ruling out alternative diagnoses, standard Brain MRI with contrast can show changes consistent with one or more of the AE anatomical syndromes (table 1 and figure 3). According to the 2016 AE clinical criteria by Graus et al, the presence of bilateral limbic encephalitis is the only MRI finding sufficient to diagnose definite AE in the correct clinical setting (eg, negative CSF viral studies) even in absence of NAAs.1 All other MRI patterns (cortical/subcortical, striatal, diencephalic, brainstem, encephalomyelitis and meningoencephalitis) can support possible or probable AE unless the NAAs panel is positive for a clinically relevant antibody.1 2 Diffuse or patchy contrast enhancement suggestive of inflammation is seen in a few patients while intense enhancing lesions are unlikely in AE.3 9 Rare findings include focal or extensive demyelination, meningeal enhancement, and rarely cortical diffusion restriction (often related to secondary seizures). Brain MRI may also be normal. Patients with initially negative MRI may show changes suggestive of AE on repeat MRI a few days later. Gadolinium should be avoided during pregnancy. Table 3 shows the main differential diagnoses for each of the AE anatomical syndromes. VIEW INLINE VIEW POPUP Table 3 Differential diagnosis of autoimmune encephalitis anatomical syndromes and suggested additional testing Figure 3 Anatomical subtypes of autoimmune encephalitis. (A) Limbic encephalitis, (B) cortical/subcortical encephalitis, (C) striatal encephalitis, (D) diencephalic encephalitis, (E) brainstem encephalitis (arrow), (F) meningoencephalitis (arrow). Importantly, brain MRI can also help exclude alternative diagnoses such as acute stroke, neoplasm or Creutzfeldt-Jacob disease (CJD), although AE MRI changes can sometimes mimic some of these entities. Unilateral, and to a lesser extent bilateral, inflammation of the mesial and non-mesial temporal lobe as well as the orbitofrontal cortex on FLAIR or DWI sequences supports herpetic encephalitis over AE.13 Parenchymal haemorrhage on gradient echo sequence is more common in herpetic encephalitis than AE although this difference did not reach statistical significance in one underpowered study comparing the two types of encephalitis.14 In some related immune-mediated conditions, the diagnosis can be inferred from typical MRI patterns such as radial perivascular enhancement in autoimmune GFAP astrocytopathy and punctate brainstem/cerebellar enhancement in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).15 16 Electroencephalogram Electroencephalogram (EEG) is commonly performed in patients with suspected AE to exclude subclinical status epilepticus in encephalopathic patients or to monitor treatment response in patients with seizures. AE is a major cause of new onset refractory status epilepticus (NORSE), which can be convulsive or non-convulsive.17 EEG can also provide evidence of focal or multifocal brain abnormality when MRI is negative which would support encephalitis over metabolic encephalopathy.1 Findings suggestive of AE include focal slowing/seizures, lateralised periodic discharges and/or extreme delta brush, which is occasionally seen in NMDAR-antibody encephalitis.18 Frequent subclinical seizures are commonly identified in LGI1-antibody encephalitis but patients may also have a normal EEG including those with classical faciobrachial dystonic seizures (FBDS).19 20 Although a normal EEG does not exclude AE, it can support primary psychiatric disorders when investigating patients with isolated new psychiatric symptoms. EEG can also help differentiate AE from CJD. Brain fluorodeoxyglucose positron emission tomography In the event of a negative brain MRI and clinical uncertainty despite high suspicion of AE, obtaining a brain fluorodeoxyglucose positron emission tomography (FDG-PET) can confirm focal or multifocal brain abnormality in the correct clinical setting.21 It can also substitute for MRI when MRI is contraindicated. In case series, brain FDG-PET was more sensitive than MRI and may reveal brain abnormalities at an earlier stage of the disease.22 Bilateral temporal hypermetabolism (in seropositive or seronegative limbic encephalitis) and bilateral occipitoparietal hypometabolism (in NMDAR-antibody encephalitis) are among the most common patterns seen and may prove useful biomarkers for specific syndromes. Importantly, further studies are needed to better differentiate AE metabolic patterns from neurodegenerative and neuroinfectious syndromes. In addition, immunosuppressants, anaesthetics and antiseizure therapies, commonly administered to AE patients, can also alter cortical metabolism. Seizures can also cause hypermetabolic changes on FDG-PET. The lack of specificity and the limited availability of FDG-PET are barriers against the wide utilisation of this technique in AE diagnosis. Aim 2: confirming an autoimmune inflammatory etiology and excluding other possibilities Following assessment for focal or multifocal brain abnormality by MRI or other studies, additional investigations are indicated to confirm AE and exclude other possibilities. Testing can be guided by the clinical-anatomical syndrome to narrow down the scope of investigations as shown in table 3. CSF analysis This is the most important test in AE evaluation and is usually the second step in the workup after brain MRI. Regardless of MRI findings, all patients with suspected encephalitis require a lumbar puncture (LP) unless there is a significant contraindication (eg, risk of herniation on brain imaging). In some cases, inflammatory CSF may be the only abnormality found on initial testing serving as the sole indication for empiric immunotherapy after infection is excluded. If timely brain MRI is not possible due to patient agitation or lack of access, clinicians should proceed with LP after a screening head CT so as not to delay immunotherapy. CSF analysis should include cell count and differential, protein, glucose, CSF/serum glucose ratio, albumin quotient, IgG index and synthesis rate, oligoclonal bands, broad viral studies including HSV1/2 PCR and varicella zoster virus (VZV) PCR and IgG/IgM, bacterial/fungal cultures when appropriate, cytology, flow cytometry, NAAs panel (eg, Autoimmune encephalopathy/encephalitis panel, etc), and in some cases, prion disorder panel (preferably RTQuIC when available). Common CSF findings in AE include mild to moderate lymphocytic pleocytosis (commonly 20–200 cells but can be as high as 900 cells with some antibodies), hyperproteinorrachia, and in some cases, elevated IgG index and/or IgG synthesis rate and positive intrathecal oligoclonal bands (unmatched in the serum).1 23 These findings in the setting of negative infectious and cytological studies support an immune-mediated aetiology but would not differentiate AE from other immune-mediated conditions (eg, neurosarcoidosis) so clinical correlation is always needed. In many patients, testing NAAs in both CSF and serum is needed because CSF detection is more sensitive for some antibodies (eg, NMDAR and GFAP antibodies) while serum is more sensitive for other antibodies (eg, onconeuronal, LGI1, and AQP4 antibodies).1 If the clinical picture is highly suggestive of an antibody with a higher serum sensitivity (eg, FBDS suggestive of LGI1-antibody encephalitis), then it might be reasonable to avoid CSF testing in clinical situations where CSF sampling is challenging. Although symptomatology can guide which neuronal antibodies (or antibody panels) to test for in some patients, it may be most practical to send the most comprehensive panel especially in patients with less defined presentations. This is because there is a significant syndromic overlap between most of these antibodies and because more than one antibody can coexist in the same patient.24 Notably, routine CSF studies may be normal in some AE patients and this does not exclude the diagnosis when other parameters are consistent with AE; therefore, testing NAAs panels is recommended in case of high clinical suspicion even if the CSF is normal.25 Blood tests In addition to testing NAAs in the serum, several blood tests are often needed to exclude other competing etiologies. Test selection can be guided by the MRI anatomical pattern as shown in table 3 but some tests may be useful in case of negative MRI such as antithyroid antibodies, toxicology screen, ammonia, vitamin B1/B12 levels, HIV, inflammatory markers, antinuclear antibodies, extractable nuclear antigen antibodies, antiphospholipid and lupus anticoagulant antibodies, immunoglobulins and metabolic and hormonal panels when appropriate.1 Monitoring sodium level is important since hyponatraemia is common with certain AE subtypes such as LGI-1 antibody encephalitis.19 Blood samples should be collected prior to treatment with intravenous immunoglobulins or plasmapheresis to avoid false positive or false negative results. Brain biopsy Most AE cases with normal brain MRI or typical MRI patterns (limbic, striatal, etc) do not require a brain biopsy. Rarely, a brain biopsy may be needed for atypical or mass-like lesions to exclude neoplastic or other possibilities especially when all other investigations point away from autoimmunity.1 Pathological findings in AE are nonspecific and include T-cell and/or B-cell perivascular and parenchymal infiltrates along with secondary gliosis.26 Aim 3: screening for an associated neoplasm It is nearly impossible to predict whether AE is paraneoplastic or non-paraneoplastic based on symptoms as both AE subtypes present similarly. Therefore, cancer screening should be considered in most adult AE patients at time of presentation.24 If the patient has a known history of cancer typically associated with paraneoplastic syndromes then a paraneoplastic aetiology is presumed, and repeat cancer screen is indicated to identify recurrence or progression. In patients with cancer history not typically associated with paraneoplastic neurologic syndromes (eg, basal cell skin cancer, prostate cancer), repeat cancer screen may unmask a new different tumour. The most common neoplasms associated with AE include small cell lung cancer, thymic neoplasm, breast cancer, ovarian teratoma or carcinoma, testicular teratoma or seminoma, neuroblastoma and lymphoma.24 In some patients, the suspicion of associated neoplasm may be high based on certain demographic factors (eg, smoking history or advanced age) or typical clinical picture (NMDAR-antibody encephalitis associated with ovarian teratoma). Although some antibodies have stronger cancer association than others (eg, antibodies against intracellular antigens), the implicated antibody is usually unknown at the time of first presentation. The following screening modalities are available: CT chest, abdomen and pelvis Initial screening with CT of the chest, abdomen and pelvis with contrast is a reasonable approach given its lower cost compared with FDG-PET and since it provides more structural details of the neoplasm (if present) to guide biopsy and further surgical intervention if indicated. A major limitation of CT-based screening is its low sensitivity for early breast and testicular cancers.24 In addition, CT is not preferred in children and pregnant women; and pelvic CT is not preferred for women in childbearing age in general. Moreover, CT contrast dye may be contraindicated due to renal impairment or dye allergy. In these situations, additional or alternative means (eg, MRI) of cancer screening are required. It is to be noted, however, that CT iodine-based dye is relatively safer in pregnant women compared with MRI gadolinium-based dye. Mammogram and breast MRI Breast cancer is a common source of paraneoplastic syndromes in females, and a mammogram should be performed if the initial CT screen is negative.24 Patients with a strong family history of breast cancer and those who are not up to date with their regular mammograms are a special concern. If mammogram is negative but the suspicion of breast cancer is high, then breast MRI may improve sensitivity of cancer detection. Pelvic or testicular ultrasound or MRI Young and middle age adults with a typical clinical picture of NMDAR-antibody encephalitis should be specifically screened for teratoma by a transvaginal or transabdominal pelvic ultrasound (or testicular ultrasound in males).24 In female patients with ataxic presentation (suggestive of PCA1/Yo antibody), pelvic ultrasound can screen for ovarian carcinoma. Likewise, in males with ataxia and other brainstem symptoms (suggestive of Ma and Kelch-like Protein-11 Antibodies), testicular ultrasound may reveal the associated neoplasm.27 Pelvic MRI may be useful if ultrasound is equivocal. Extraovarian and extratesticular germ cell tumours may be detected on CT-based or MRI-based general cancer screening. Whole body FDG-PET scan Whole body FDG-PET can be more sensitive for early neoplasms when initial CT screen is negative or inconclusive and the suspicion of cancer is high (eg, smoker elderly patient, classic paraneoplastic presentation).24 It can also be used as the initial screening tool when there is a contraindication to high resolution CT or iodine contrast. Insurance coverage can be an obstacle and insurers should consider fewer restrictions on FDG-PET in AE patients given the high likelihood of a coexisting cancer in those patients. Section 2: acute treatment Intensive care unit needs The main indications for intensive care unit (ICU) admission in AE include refractory status epilepticus, severe dysautonomia and respiratory compromise (eg, from brainstem involvement, associated neuromuscular syndrome or medication-induced hypoventilation).28 It is important for ICU clinicians to distinguish central non-infectious fevers caused by the primary disease from infectious processes. Careful monitoring and management of blood pressure and heart rate fluctuations is critical in patients with severe dysautonomia. A temporary pacemaker may be needed in patients with severe dysrhythmia until the dysautonomia improves. Patients with severe hyponatraemia may require controlled slow correction of sodium levels to avoid central pontine myelinolysis. In most cases, hyponatraemia is related to inappropriate antidiuretic hormone secretion and fluid restriction is sufficient. In rare occasions with massive inflammation and brain oedema, intracranial pressure monitoring and management may be indicated. AE patients are often subject to high doses of sedation, antiseizure medications, and other symptomatic therapies so monitoring for drug toxicity in the ICU is imperative. Empiric antimicrobial treatment In many encephalitis patients, differentiating infectious from autoimmune aetiologies may be difficult prior to CSF analysis and therefore starting empiric antimicrobials with CNS coverage is always recommended until infection is excluded. The common practice is to start CNS doses of intravenous acyclovir and standard coverage for bacterial meningitis. Antibiotics and acyclovir can later be discontinued if CSF bacterial and HSV/VZV studies return negative. Acute immunotherapy Several retrospective studies have shown that early and aggressive immunotherapy is associated with better outcomes in AE patients.1 29 The 2016 AE clinical criteria emphasise the importance of starting immunotherapy once AE is highly suspected and infectious etiologies are excluded based on CSF results (cell-count, glucose, viral PCR, gram stain). It is impractical and potentially hazardous to delay immunotherapy until AE is confirmed by a positive antibody. There are no robust clinical trials comparing the different modalities of acute immunotherapy; therefore, the choice of the initial therapy may be based on anecdotal evidence and factors related to the specific syndromic presentation and comorbidities as shown in figure 4 and detailed below: Figure 4 Therapeutic algorithm for autoimmune encephalitis. *Relative contraindications to steroids include uncontrolled hypertension, uncontrolled diabetes, acute peptic ulcer and severe behavioural symptoms that worsen with corticosteroid therapy. **Steroid-responsive conditions include faciobrachial dystonic seizures suggestive of LGI1-antibody encephalitis, autoimmune encephalitis in the setting of immune checkpoint inhibitors, central demyelination, autoimmune GFAP astrocytopathy, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, and steroid-responsive encephalopathy associated with autoimmune thyroiditis. ***High thromboembolic risk includes patients with known or suspected cancer, smoking history, hypertension, diabetes, hyperlipidaemia and hypercoagulable states. Ab, antibody; AE, autoimmune encephalitis; Ag, antigen; IVMP, intravenous methylprednisolone; IVIg, intravenous Ig; IL-6: interleukin 6; NORSE, new-onset refractory status epilepticus; PLEX, plasma exchange. High-dose corticosteroids Empiric treatment with intravenous methylprednisolone at a dose of 1 g per day for 3–7 days is a common reasonable approach to achieve initial immunosuppressive and anti-inflammatory effect in AE patients.1 It is also the preferred approach in presentations known to be specifically corticosteroid-responsive namely demyelinating pattern on MRI (suggestive of AE overlap with demyelinating syndromes),30 or dotted or radial enhancement (suggestive of CLIPPERS or autoimmune GFAP astrocytopathy, respectively).15 16 Patients with FBDS suggestive of LGI1-antibody encephalitis may also show a dramatic response to corticosteroids.19 Patients with known or highly suspected paraneoplastic AE associated with classical onconeuronal antibodies are thought to have a primarily T-cell mediated inflammation making corticosteroids, theoretically, a preferred option for immunosuppression over intravenous IG or plasma exchange (PLEX). However, paraneoplastic conditions associated with classical onconeuronal antibodies are often resistant to immunosuppression and tend to respond best to cancer therapy. A notable exception are patients who develop accelerated paraneoplastic AE in the setting of ICI treatment. These patients may be particularly responsive to corticosteroids given their inhibitory effect on T-cell overactivity which is the pathogenic hallmark of ICI-associated immune adverse events; however, second-line therapies may also be needed in some cases.12 On our AEACN survey, 84% of responders chose corticosteroids alone (65%) or in combination with other agents (19%) for initial immunotherapy in patients with a general AE presentation. Likewise, 74% of responders chose corticosteroids for initial immunotherapy for patients presenting with FBDS suggestive of LGI1-antibody encephalitis, alone (58%) or in combination with other agents (16%). For NMDAR-antibody encephalitis, corticosteroids remained the most popular choice on the survey. However, the percentage was lower selected only by 63% of responders either alone (35%) or combined with other agents (28%) indicating a larger diversity among specialists when selecting first-line therapy in those patients. Similar diversity was present for treatment of known or highly suspected paraneoplastic AE; whereas corticosteroids remained the most popular choice, it was chosen by only 48.5% of responders, alone (29%) or combined with other agents (19%) (see online supplemental document S2). One theoretical disadvantage to corticosteroids in AE is their potential for causing initial worsening of behavioural/psychiatric symptoms hampering a timely evaluation of treatment response although in most cases, corticosteroids may actually improve these symptoms. The use of corticosteroids may also be difficult in patients with common comorbidities such as uncontrolled hypertension or diabetes. Some experts recommend avoiding corticosteroids in patients with known GAD65-antibody associated neurological syndromes for fear of inducing type-1 diabetes but this concern remains theoretical without confirmatory studies. In patients with atypical or mass-like lesions on brain MRI in whom primary CNS lymphoma is on the differential diagnosis, corticosteroids should be delayed so as not to interfere with pathology results if a biopsy is considered during hospitalisation. Similar precautions are advisable when systemic autoimmunity such as sarcoidosis is on the differential. Intravenous Ig Intravenous Ig (IVIg) at a dose of 2 g/kg over 2–5 days is a relatively easy-to-use and timely option for fast immunomodulation when corticosteroids are contraindicated or when the clinical picture is suggestive of or known to be related to antibody-mediated disease (eg, probable or definite NMDAR-antibody encephalitis).29 IVIg can be more readily available than PLEX in some centres and it does not require a central line. A recent randomised blinded study showed IVIg efficacy over placebo in controlling seizures in a small number of patients with LGI1-antibody and CASPR2-antibody AE.31 On our AEACN survey, IVIg was the most popular acute immunotherapy if corticosteroids are contraindicated chosen by 41% of responders. Also 40% of responders indicated choosing IVIg alone or in combination with corticosteroids and other immunotherapies for acute therapy if the clinical picture was suggestive of NMDAR-antibody encephalitis. A downside to IVIg is its association with increased thromboembolic risk. Therefore, IVIg should be used with caution in patients with known or suspected paraneoplastic AE or other risk factors for thrombosis (eg, heavy smokers and the elderly). In addition, the aetiology of paraneoplastic AE associated with antibodies against intracellular antigens is thought to be cell-mediated rather than antibody-mediated rendering the use of IVIg in this setting potentially ineffective. On our survey only 25% of responders indicated using IVIg in known or suspected paraneoplastic AE. The use of IVIg may also worsen coexisting hyponatraemia due to volume expansion, which may potentially predispose to brain oedema and worsening mental status.32 Plasma exchange PLEX (5–10 sessions every other day) is an effective option for acute immunomodulation when corticosteroids are contraindicated or ineffective. In a small retrospective study, patients with NMDAR-antibody encephalitis treated with both corticosteroids and PLEX had better improvement in the modified Rankin score than those treated with corticosteroids alone,33 which is similar to the results in other antibody-mediated conditions like NMOSD.34 PLEX may be particularly effective in AE cases with associated central demyelination or coexisting NMOSD. It provides a potentially faster immunomodulation in patients with severe or fulminant presentations. It has no known psychiatric side effects and does not increase the risk of thromboembolism except for line-related thrombosis. Major limitations include increased bleeding risk, volume shifts (which can be problematic in dysautonomic patients), and the need for central line placement (in some institutions) with its associated risks. In addition, it is less suitable for agitated patients. Combined first-line therapies If the initial clinical picture is severe (eg, NMDAR-antibody encephalitis, NORSE, severe dysautonomia), clinicians may consider using combined first-line therapies from the beginning despite the lack of high quality evidence to support this practice. On our AEACN survey, combination therapy was the second most popular choice after corticosteroids alone if the clinical picture was suggestive of NMDAR-antibody encephalitis chosen by 28% of responders, and for unspecified AE (19%). More commonly, combination therapy is done sequentially if there is no meaningful response to the initial agent (eg, adding IVIg and/or PLEX after completing corticosteroids). On the survey, 62% of responders chose adding a different first-line therapy if the initial agent was ineffective while 26% chose going directly to a second-line agent. Other options like adding a second round or prolonging the duration of the same first-line agent were less popular. Second line agents If there is no meaningful clinical or radiological response to optimised first-line therapy after 2–4 weeks, the addition of a second-line agent with both rapid and sustained immunosuppressive effects can improve the outcome.29 However, the exact definition and timing of treatment responsiveness is not well defined and some clinicians may anecdotally choose earlier initiation of second-line agents. Both rituximab and cyclophosphamide have been used as second-line agents for rescue therapy in AE with good results.29 Rituximab is less toxic than cyclophosphamide and therefore is preferentially considered by most clinicians although it may not be as effective for cell-mediated inflammation as in the case of antibodies against intracellular antigens. However, although rituximab acts mainly on B-cells, it indirectly suppresses T-cell activity by reducing B-cell drive to T-cells. In most newly diagnosed cases, it is hard to determine clinically whether AE is antibody or cell-mediated before the antibody results are available. Some clues may help the clinician come to a preliminary hypothesis regarding aetiology (eg, FBDS or typical NMDAR-antibody encephalitis presentation suggest antibody-mediated AE while patients with known or increased cancer risk are more likely to have cell-mediated AE). Based on these clues, clinicians may decide to use rituximab or cyclophosphamide as a second-line agent if antibody results are delayed or if there is no access to antibody testing. Common rituximab dosing regimens include 375 mg/m2 weekly for 4 weeks or two doses of 1000 mg 2 weeks apart. Common dosing regimen of cyclophosphamide include 600–1000 mg/m2. A few case series have shown response to proteasome inhibitors that block plasma-cell generation (bortezomib), interleukin (IL)-6 inhibition (tocilizumab), or low dose IL-2 in patients who did not respond quickly to conventional second-line agents.35–37 However, the evidence behind these non-conventional rescue therapies remains limited and more research is needed to confirm their effectiveness in refractory AE. A clinical trial of ocrelizumab (a humanised anti-CD20 monoclonal antibody with a similar mechanism of action to rituximab) is currently recruiting, and a clinical trial of bortezomib is underway (www.clinicaltrials.gov, accessed 13 April 2020). When a second-line agent is used in the acute setting, it also serves as a bridging therapy to prevent early relapses that might happen if immunosuppression is abruptly discontinued.38 Prognostication and clinical severity tools are being developed to help select patients who would benefit from conventional and non-conventional second-line agents such as the anti-NMDAR Encephalitis 1-year Functional Status score and the Clinical Assessment Scale in Autoimmune Encephalitis.39 40 On the AEACN survey, 50% of responders indicated they would consider adding a second-line agent in the acute setting only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in the acute setting on all patients regardless of the response to first-line therapy. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies and no clinical clues for aetiology. Conclusion In this first part of the best practice recommendations, we covered the clinical presentation, diagnostic workup and acute management of AE guided by published studies and the results of the AEACN survey providing updated recommendations for management of patients with suspected AE. The second part will follow with a focus on bridging therapy, symptomatic treatment and maintenance immunotherapy. A discussion of the limitations will be presented at the end of the second part. A summary of the best practice recommendations for AE diagnosis and acute management is presented in box 1. Box 1 Best practice recommendations summary for acute management of autoimmune encephalitis (AE) Evaluate the likelihood of AE relative to the patient’s clinical picture. Perform brain MRI and/or EEG to look for focal or multifocal brain abnormality. Perform lumbar puncture to support inflammatory aetiology and rule out infective/neoplastic causes. Test oligoclonal bands, IgG index, IgG synthesis rate and neuronal autoantibodies in the cerebrospinal fluid (CSF). Send blood tests to rule out other potential causes guided by neuroanatomical and clinical data. Test neuronal autoantibodies in the serum. Consider brain FDG-PET when there is a high clinical suspicion of AE and other paraclinical studies are uninformative. Perform cancer screening with CT chest, abdomen, and pelvis with contrast in relevant cases (or MRI when CT is contraindicated or not preferred). If negative, consider further testing with mammogram/breast MRI, pelvic ultrasound, and/or whole body FDG-PET guided by the clinical presentation and each patient’s specific cancer risk factors. Once infection is ruled out based on basic CSF results (eg, number of cells) and if biopsy for primary CNS lymphoma or neurosarcoidosis is not a consideration, start acute immunotherapy with high dose corticosteroids (or IVIG or PLEX if steroids are not preferred or contraindicated). If there is no clinical, radiological or electrophysiological improvement by the end of the initial treatment cycle, add IVIG or PLEX. Consider IVIG first in agitated patients and in those with bleeding disorders. Consider PLEX first in patients with severe hyponatraemia, high thromboembolic (or cancer) risk, and if there is associated brain or spinal demyelination. Consider starting with a combination therapy of steroids/IVIG or steroids/PLEX from the beginning (as opposed to sequentially) in patients with severe initial presentation (eg, severe NMDAR-antibody presentation, new onset refractory status epilepticus, severe dysautonomia, etc). If there is no clinical or radiological improvement 2–4 weeks after completion of combined acute therapy, consider starting a second-line agent when the clinical suspicion is high and/or a clinically relevant antibody is present. Consider rituximab in known or highly suspected antibody-mediated autoimmunity (eg, NMDAR-antibody encephalitis) and consider cyclophosphamide in known or highly suspected cell-mediated autoimmunity (eg, classical paraneoplastic syndrome). If no clear objective or subjective evidence of improvement with conventional second-line therapies, consider novel approaches such as tocilizumab or bortezomib although there is only minimal evidence to support their use. Start bridging therapy with gradual oral prednisone taper or monthly intravenous Ig or intravenous methylprednisolone. Avoid steroid taper or implement a shorter taper in vague cases with poor response to initial immunosuppressive therapy or when immunosuppression may impose higher risks than benefits (eg, patients with cancer or active infection). Ethics statements Patient consent for publication Not required. Acknowledgments The authors would like to thank Kimberley de Haseth, Director of Programs at the Autoimmune Encephalitis Alliance for coordinating the communication between the AEACN members and for distributing the survey. References ↵ Graus F , Titulaer MJ , Balu R , et al . A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.doi:10.1016/S1474-4422(15)00401-9 pmid:http://www.ncbi.nlm.nih.gov/pubmed/26906964 OpenUrlCrossRefPubMed ↵ Dalmau J , Graus F . Antibody-Mediated encephalitis. N Engl J Med 2018;378:840–51.doi:10.1056/NEJMra1708712 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29490181 OpenUrlCrossRefPubMed ↵ Heine J , Prüss H , Bartsch T , et al . Imaging of autoimmune encephalitis--Relevance for clinical practice and hippocampal function. Neuroscience 2015;309:68–83.doi:10.1016/j.neuroscience.2015.05.037 pmid:http://www.ncbi.nlm.nih.gov/pubmed/26012492 OpenUrlCrossRefPubMed ↵ Singh TD , Fugate JE , Rabinstein AA . The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology 2015;84:359–66.doi:10.1212/WNL.0000000000001190 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25540320 OpenUrlCrossRefPubMed ↵ Graus F , Elkon KB , Lloberes P , et al . Neuronal antinuclear antibody (anti-Hu) in paraneoplastic encephalomyelitis simulating acute polyneuritis. Acta Neurol Scand 1987;75:249–52.doi:10.1111/j.1600-0404.1987.tb07928.x pmid:http://www.ncbi.nlm.nih.gov/pubmed/3035860 ↵ Lancaster E . Paraneoplastic disorders. Continuum 2017;23:1653–79.doi:10.1212/CON.0000000000000542 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29200116 OpenUrlPubMed ↵ Dubey D , Pittock SJ , Kelly CR , et al . Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018;83:166–77.doi:10.1002/ana.25131 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29293273 OpenUrlCrossRefPubMed ↵ López-Chiriboga AS , Clardy SL . Emerging subspecialties in neurology: autoimmune neurology. Neurology 2017;89:e129–33.doi:10.1212/WNL.0000000000004356 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28894037 OpenUrlCrossRefPubMed ↵ Abboud H , Rossman I , Mealy MA , et al . Neuronal autoantibodies: differentiating clinically relevant and clinically irrelevant results. J Neurol 2017;264:2284–92.doi:10.1007/s00415-017-8627-4 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28975404 OpenUrlCrossRefPubMed ↵ Mittal MK , Rabinstein AA , Hocker SE , et al . Autoimmune encephalitis in the ICU: analysis of phenotypes, serologic findings, and outcomes. Neurocrit Care 2016;24:240–50.doi:10.1007/s12028-015-0196-8 pmid:http://www.ncbi.nlm.nih.gov/pubmed/26319044 OpenUrlCrossRefPubMed ↵ López-Chiriboga AS , Flanagan EP . Diagnostic and therapeutic approach to autoimmune neurologic disorders. Semin Neurol 2018;38:392–402.doi:10.1055/s-0038-1660819 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30011418 OpenUrlCrossRefPubMed ↵ Kumar N , Abboud H . Iatrogenic CNS demyelination in the era of modern biologics. Mult Scler 2019;25:1079–85.doi:10.1177/1352458519828601 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30767720 OpenUrlCrossRefPubMed ↵ Oyanguren B , Sánchez V , González FJ , et al . Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies. Eur J Neurol 2013;20:1566–70.doi:10.1111/ene.12249 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23941332 OpenUrlCrossRefPubMed ↵ Chow FC , Glaser CA , Sheriff H , et al . Use of clinical and neuroimaging characteristics to distinguish temporal lobe herpes simplex encephalitis from its mimics. Clin Infect Dis 2015;60:1377–83.doi:10.1093/cid/civ051 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25637586 OpenUrlCrossRefPubMed ↵ Fang B , McKeon A , Hinson SR , et al . Autoimmune glial fibrillary acidic protein Astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol 2016;73:1297–307.doi:10.1001/jamaneurol.2016.2549 pmid:http://www.ncbi.nlm.nih.gov/pubmed/27618707 OpenUrlPubMed ↵ Tobin WO , Guo Y , Krecke KN , et al . Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain 2017;140:2415–25.doi:10.1093/brain/awx200 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29050399 OpenUrlCrossRefPubMed ↵ Gaspard N , Foreman BP , Alvarez V , et al . New-Onset refractory status epilepticus: etiology, clinical features, and outcome. Neurology 2015;85:1604–13.doi:10.1212/WNL.0000000000001940 pmid:http://www.ncbi.nlm.nih.gov/pubmed/26296517 OpenUrlCrossRefPubMed ↵ Steriade C , Moosa ANV , Hantus S , et al . Electroclinical features of seizures associated with autoimmune encephalitis. Seizure 2018;60:198–204.doi:10.1016/j.seizure.2018.06.021 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30031297 OpenUrlCrossRefPubMed ↵ Irani SR , Michell AW , Lang B , et al . Faciobrachial dystonic seizures precede LGI1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900.doi:10.1002/ana.22307 pmid:http://www.ncbi.nlm.nih.gov/pubmed/21416487 ↵ Aurangzeb S , Symmonds M , Knight RK , et al . Lgi1-Antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures. Seizure 2017;50:14–17.doi:10.1016/j.seizure.2017.05.017 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28586706 OpenUrlCrossRefPubMed ↵ Probasco JC , Solnes L , Nalluri A , et al . Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2017;4:e352. doi:10.1212/NXI.0000000000000352 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28567435 ↵ Solnes LB , Jones KM , Rowe SP , et al . Diagnostic Value of 18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis. J Nucl Med 2017;58:1307–13.doi:10.2967/jnumed.116.184333 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28209905 ↵ Blinder T , Lewerenz J . Cerebrospinal fluid findings in patients with autoimmune Encephalitis-A systematic analysis. Front Neurol 2019;10:804. doi:10.3389/fneur.2019.00804 pmid:http://www.ncbi.nlm.nih.gov/pubmed/31404257 OpenUrlCrossRefPubMed ↵ Titulaer MJ , Soffietti R , Dalmau J , et al . Screening for tumours in paraneoplastic syndromes: report of an EFNS Task force. Eur J Neurol 2011;18:19–e3.doi:10.1111/j.1468-1331.2010.03220.x pmid:http://www.ncbi.nlm.nih.gov/pubmed/20880069 OpenUrlCrossRefPubMed ↵ Escudero D , Guasp M , Ariño H , et al . Antibody-Associated CNS syndromes without signs of inflammation in the elderly. Neurology 2017;89:1471–5.doi:10.1212/WNL.0000000000004541 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28878050 OpenUrlCrossRefPubMed ↵ Maat P , de Beukelaar JW , Jansen C , et al . Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease. Neurol Neuroimmunol Neuroinflamm 2015;2:e178. doi:10.1212/NXI.0000000000000178 pmid:http://www.ncbi.nlm.nih.gov/pubmed/26601117 ↵ Mandel-Brehm C , Dubey D , Kryzer TJ , et al . Kelch-Like protein 11 antibodies in Seminoma-Associated paraneoplastic encephalitis. N Engl J Med 2019;381:47–54.doi:10.1056/NEJMoa1816721 pmid:http://www.ncbi.nlm.nih.gov/pubmed/31269365 OpenUrlCrossRefPubMed ↵ Harutyunyan G , Hauer L , Dünser MW , et al . Autoimmune encephalitis at the neurological intensive care unit: etiologies, reasons for admission and survival. Neurocrit Care 2017;27:82–9.doi:10.1007/s12028-016-0370-7 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28028790 OpenUrlPubMed ↵ 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;12:157–65.doi:10.1016/S1474-4422(12)70310-1 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23290630 ↵ Titulaer MJ , Höftberger R , Iizuka T , et al . Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014;75:411–28.doi:10.1002/ana.24117 pmid:http://www.ncbi.nlm.nih.gov/pubmed/24700511 OpenUrlCrossRefPubMed ↵ Dubey D , Britton J , McKeon A , et al . Randomized placebo-controlled trial of intravenous immunoglobulin in autoimmune LGI1/CASPR2 epilepsy. Ann Neurol 2020;87:313–23.doi:10.1002/ana.25655 pmid:http://www.ncbi.nlm.nih.gov/pubmed/31782181 OpenUrlCrossRefPubMed ↵ Nguyen MK , Rastogi A , Kurtz I . True hyponatremia secondary to intravenous immunoglobulin. Clin Exp Nephrol 2006;10:124–6.doi:10.1007/s10157-006-0416-9 pmid:http://www.ncbi.nlm.nih.gov/pubmed/16791398 OpenUrlCrossRefPubMed ↵ DeSena AD , Noland DK , Matevosyan K , et al . Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-N-methyl-D-aspartate receptor antibody encephalitis: a retrospective review. J Clin Apher 2015;30:212–6.doi:10.1002/jca.21363 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25664728 OpenUrlCrossRefPubMed ↵ Abboud H , Petrak A , Mealy M , et al . Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler 2016;22:185–92.doi:10.1177/1352458515581438 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25921047 OpenUrlCrossRefPubMed ↵ Scheibe F , Prüss H , Mengel AM , et al . Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology 2017;88:366–70.doi:10.1212/WNL.0000000000003536 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28003505 OpenUrlCrossRefPubMed ↵ Lee W-J , Lee S-T , Moon J , et al . Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics 2016;13:824–32.doi:10.1007/s13311-016-0442-6 pmid:http://www.ncbi.nlm.nih.gov/pubmed/27215218 OpenUrlCrossRefPubMed ↵ Lim J-A , Lee S-T , Moon J , et al . New feasible treatment for refractory autoimmune encephalitis: low-dose interleukin-2. J Neuroimmunol 2016;299:107–11.doi:10.1016/j.jneuroim.2016.09.001 pmid:http://www.ncbi.nlm.nih.gov/pubmed/27725107 OpenUrlCrossRefPubMed ↵ Nosadini M , Mohammad SS , Ramanathan S , et al . Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother 2015;15:1391–419.doi:10.1586/14737175.2015.1115720 pmid:http://www.ncbi.nlm.nih.gov/pubmed/26559389 OpenUrlCrossRefPubMed ↵ Balu R , McCracken L , Lancaster E , et al . A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis. Neurology 2019;92:e244–52.doi:10.1212/WNL.0000000000006783 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30578370 OpenUrlCrossRefPubMed ↵ Lim J-A , Lee S-T , Moon J , et al . Development of the clinical assessment scale in autoimmune encephalitis. Ann Neurol 2019;85:352–8.doi:10.1002/ana.25421 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30675918 OpenUrlCrossRefPubMed
Scooped by Nesrin Shaheen
Scoop.it!

Topiramate as Possible Treatment for Catatonia in Anti-NMDA Receptor Encephalitis | American Journal of Psychiatry Residents' Journal

Topiramate as Possible Treatment for Catatonia in Anti-NMDA Receptor Encephalitis | American Journal of Psychiatry Residents' Journal | AntiNMDA | Scoop.it
Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is a disorder characterized by the presence of pathological auto-antibodies, frequently paraneoplastic, and presenting primarily in young...
No comment yet.