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Tardive syndromes | Practical Neurology

Tardive syndromes | Practical Neurology | AntiNMDA | Scoop.it
From pn.bmj.com - October 14, 2020 11:52 AM
INTRODUCTION Movement disorders developing as a direct consequence of the administration of dopamine receptor-blocking neuroleptic drugs were first reported in 1957, 5 years after their introduction into psychiatric practice. The year 1964 saw the first collective description of these movement disorders as a ‘tardive’ (from the latin tardus, meaning late) phenomenon,1 reflecting their delayed onset following medication administration, in contrast to ‘acute’ dystonic reactions, which also follow dopaminergic blockade. This term was rapidly adopted, and in the following decades, a flurry of publications were to expand the phenotypic spectrum of the disorder. Concurrently, theories aiming to explain disease pathogenesis began to emerge, and several therapeutic strategies were explored. This review provides physicians with a pragmatic, clinically based platform with which to approach tardive syndromes. In addition, we explore recent developments in our understanding of disease pathophysiology, discuss how to approach treatment of tardive syndromes and try to dispel some commonly held myths. The nosology of tardive syndromes is plagued by inconsistent use of descriptive language. The term ‘tardive dyskinesia’, when first introduced, was intended to subsume the range of diverse movements that can emerge in a delayed fashion following long-term neuroleptic administration. However, more recently, a less confusing approach which classifies tardive movements according to their clinical phenomenology has been promoted, and will be used in this review. Accordingly, we use ‘tardive syndrome’ as the umbrella term for any/all potential tardive movement disorders but reserve ‘tardive dyskinesia’ as a descriptor of a specific clinical entity, namely the characteristic oro-bucco-lingual choreiform movements (see The ‘typical’ tardive syndrome). The scale of the problem Tardive syndromes are a predictable, sometimes permanent, disabling consequence of medication administration. They occur predominantly in the psychiatric population, where they exacerbate the burden of social stigma and are linked to poorer quality of life and increased morbidity and mortality.2 3 Antipsychotic drugs are by far the most common offenders, though numerous others have also been implicated (table 1). VIEW INLINE VIEW POPUP Table 1 Examples of medications known to cause tardive syndromes4–11 Tardive syndromes affect 20%–50% of patients receiving neuroleptic drugs.12 Advancing age is the most robust risk factor, with incidence increasing from 5% per annum in those aged under 40 years to 12% or more per annum in older age groups.12–14 The risk increases cumulatively with duration of exposure and medication dose, with a cumulative incidence rate of 20%–25% after 5 years of exposure.15-17 Note however that the medication compliance rate in patients with schizophrenia is around 50%, so these figures may well be an underestimate.18 Numerous other factors may further increase the risk, including history of an affective disorder, previous organic brain damage, diabetes mellitus, female sex (oestrogen perhaps being protective premenopausally) and race.19 Indeed, disease prevalence is lower on average in Asians (roughly 20%) and higher on average in African–Americans compared with Caucasians.19–21 Disease pathophysiology The pathophysiological basis of tardive syndromes remains poorly understood, as reflected in the large number of theories purporting to explain the delayed development of these movement disorders. The earliest theory to gain popular acceptance was the so-called dopamine receptor hypersensitivity theory. This suggested that dopamine-blocking neuroleptics led to compensatory upregulation and/or hypersensitivity of postsynaptic dopamine (particularly D2) receptors.22 23 Hypersensitivity of these receptors, which are expressed on indirect pathway medium spiny neurones and are inhibitory, would have the net effect of pallidal and subthalamic nucleus disinhibition, producing abnormal hyperkinetic movements.22 This hypothesis was largely based on clinical observations, such as the greater likelihood of tardive syndromes in patients receiving potent D2 blockers and the apparent improvement in tardive dyskinesia with additional dopaminergic blockade, as well as on some animal studies.22 23 However, evidence in humans for such alterations is lacking. There is no correlation between in vivo striatal D2 receptor ligand binding assessed by positron emission tomography and the severity of tardive dyskinesia. Equally, postmortem examinations have not demonstrated significant differences in D2 receptor numbers in those with and without tardive syndromes.22 Moreover, this theory does not explain why many patients do not recover after they stop the offending medication; if the only problem were receptor upregulation/hypersensitivity, one would expect this to normalise following drug withdrawal. An alternative hypothesis is that tardive syndromes actually represent a neurodegenerative disorder of striatal interneurones induced by oxidative stress. This theory, which is supported by animal and human neuropathological studies,24 25 holds that dopaminergic receptor blockade causes increased dopamine turnover and oxygen free radical production by monoamine oxidase.22 These free radicals are thought to be toxic to striatal interneurones, causing gliosis within the basal ganglia, thus explaining why the symptoms persist after stopping the medication. However, the significant and sustained improvement that sometimes follows deep-brain stimulation for tardive syndromes might argue against this idea. A further theory implicates damaged or dysfunctional striatal gamma-aminobutyric acid (GABA)ergic neurones in the pathogenesis of tardive dyskinesia. These neurones synapse on the soma of medium spiny neurones, providing potent feedforward inhibition, balancing activity in the direct and indirect basal ganglia pathways, and providing surround inhibition.22 23 Selective lesioning of these neurones produces dyskinesia.26 Long-term D2 agonism, in theory, could potentially damage GABAergic interneurones via glutamate-mediated excitotoxicity and increased oxidative stress from dopamine turnover.27 Finally, altered N-methyl-D-aspartate (NMDA)-mediated synaptic plasticity may provide a unifying theory. Antipsychotics are known to influence NMDA receptor-mediated synaptic plasticity. In this setting, patterns of abnormal neurotransmission, for example, secondary to D2 receptor hypersensitisation could be abnormally potentiated, perpetuating a cycle of abnormal sensorimotor integration and abnormal tardive movements.22 Of course, not everyone who is exposed to neuroleptic drugs develops a tardive syndrome, implying that other, possibly genetic factors are at play, conferring increased vulnerability to tardive syndromes. Genome-wide association studies have identified some potential candidate genes, though their relevance to clinical practice remains unclear.28 Making the diagnosis: the devil is in the detail This section describes the typical (or perhaps simply better recognised) and less typical presentations of tardive syndromes. One must be mindful however that individual components of the syndrome rarely occur in isolation, but rather generally coexist to greater or lesser degrees (though one may be dominant). A confident diagnosis often depends on identifying multiple movement phenomena that are compatible with a tardive syndrome. Thus, an important part of the evaluation involves not only identifying a movement of potentially tardive aetiology, but actively searching for the presence of other compatible abnormalities. Failing to notice clues, such as a fidgety patient (akathisia) who sighs deeply (respiratory dyskinesia) and moves his legs back and forth during the consultation (stereotypies), can rapidly lead one down the wrong diagnostic path. Although diagnostic criteria for tardive syndromes have been developed (table 2), only three questions matter in clinical practice: Is there a history of taking a dopamine receptor-blocking or other tardive syndrome-causing drug, as prescription medication, over-the-counter/traditional remedies or poisoning? What is the temporal relationship of taking this drug intake to the onset of the movement disorder? Is the clinical phenomenology compatible with a tardive syndrome (see below)? VIEW INLINE VIEW POPUP Table 2 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) definition of tardive syndromes The ‘typical’ tardive syndrome ‘Classic’ tardive dyskinesia involves stereotyped choreoathetoid movements predominantly involving the lips, tongue and perioral region. The movements often predominate in the lower face, with frontalis involvement being unusual. Patients often move the tongue in a writhing motion inside the mouth, are prone to frequent rapid tongue protrusion (‘flycatcher tongue’) and pushing of the tongue against the inside of the cheek, creating a bulge (‘bonbon sign’). Chewing and/or grimacing movements, lip smacking and puckering are typical. This may be accompanied by low amplitude choreiform movements of the distal limbs, the so-called ‘piano player dyskinesia’, resembling finger movements on piano keys.29 Patients are often unaware of these involuntary movements, though those involving the lips and tongue may cause problems with feeding. Tardive dyskinesia is usually accompanied by one or more of the following tardive phenomena: Tardive akathisia This is an uncomfortable sense of inner restlessness, requiring the affected individual to repeatedly move about in order to ease the unpleasant sensation. Movements can include rocking in one place when seated, marching when standing, repetitively scratching or rubbing, or just appearing generally ‘fidgety’ during the consultation. Tardive stereotypies These are patterned, purposeless, repetitive and somewhat ritualistic movements that may appear as truncal rocking, pelvic thrusting, to-and-fro leg movements, hand-wringing or crossing/uncrossing of the legs. They may outwardly resemble akathisia but are not accompanied by inner restlessness. Tardive dystonia As with most tardive syndromes, tardive dystonia adopts distinct phenomenological characteristics which are easily identified by the trained observer. The disorder frequently involves the craniocervical region, manifesting as retrocollis. Dystonia may extend to the trunk as opisthotonic posturing, while in the arms, abduction, internal rotation and wrist flexion is the classically adopted posture.29 Blepharospasm may also emerge. In contrast to other tardive syndromes, tardive dystonia is particularly common in young men aged around 40 years.24 Remission is also less likely than with tardive dyskinesia, particularly with drug exposure beyond 10 years.24 The following tardive disorders are less well defined, with only a handful of reported cases. Tardive tourettism This rare disorder manifests as multiple motor and verbal tics that emerge after exposure to dopamine receptor-blocking agents. The tics generally resemble those of primary tic disorders, exhibiting suppressibility, build-up of tension before the tic and release of tension afterwards.30 31 Tardive tremor This was first proposed as an entity in a 1992 report of five patients with a 3–5 Hz postural and action greater than rest tremor but without parkinsonism.32 Although similar to parkinsonian tremor, tardive tremor is distinguished by its postural and kinetic (rather than rest) predominance, its coarse disabling nature, its lack of levodopa responsiveness and its occasional improvement with further dopaminergic blockade or tetrabenazine.32 33 The syndrome generally persists despite withdrawal of dopamine receptor-blocking agents. Tardive myoclonus This describes brief, upper-limb predominant postural myoclonic movements that are said to result from long-term dopaminergic blockade.34 35 However, there is only very limited literature on this entity, which should therefore be interpreted with caution.34 35 Tardive gait This is a poorly characterised and non-uniform phenomenon, with gait disturbances having been described as ‘dancing’ (multiple short steps followed by a long step) or ‘duck-like’ (broad based with short stride length and some steppage features). Other abnormalities include walking with initial floor contact with toes rather than heels, spastic qualities and abnormal arm swing.36 Some ‘atypical’ presentations Patients with tardive syndromes not infrequently exhibit other less recognised, but nonetheless characteristic features that point towards the diagnosis. Among these, the most important are respiratory phenomena, tardive Pisa syndrome and withdrawal emergent dyskinesia. Respiratory dyskinesia First described in 1964, respiratory dyskinesia involves periodic disturbances of ventilatory rate, rhythm and amplitude, sometimes with ventilatory pauses or forced inspiration against a closed glottis.37 Patients may complain of dyspnoea or dysphonia, or may be seen to huff, grunt, gasp or take short, rapid breaths.38 These phenomena often accompany other more classic tardive motor features. Tardive Pisa syndrome This phenomenon, predominantly affecting older women, describes a drug-induced persistent truncal dystonia manifesting as tonic lateral flexion, occasionally with slight rotation.39 The ‘laterally leaning patient’ is an important clue to a tardive aetiology. Withdrawal emergent dyskinesia This syndrome is considered a variant of tardive dyskinesia, which generally develops after either abruptly stopping or significantly reducing the dose of neuroleptic medications.40 It predominantly affects children and usually manifests as generalised chorea (as opposed to the facial-predominant movements observed in classic tardive dyskinesia). It is usually self-limiting and resolves after days to weeks.40 Tardive oculogyric crises Oculogyric crises were originally described as being characteristic of encephalitis lethargica, although now they are more commonly associated with medication-related acute dystonic reactions (as well as dopamine synthesis pathway defects). However, oculogyric crises can also rarely develop as a tardive phenomenon in patients chronically exposed to antipsychotic medications.41 42 Tardive oculogyric crises often accompany other tardive motor phenomena and may go unrecognised. They are sometimes associated with transient recurrences of psychiatric symptoms, including anxiety, auditory hallucinations and bizarre behaviour.41 Tardive pain syndromes A variety of tardive pain syndromes have also been described, temporally associated with neuroleptic use and often responding to standard tardive syndrome treatments. Examples include tardive oral pain, which describes an uncomfortable, often burning sensation in the mouth and lips, and painful genital syndrome, with similar affliction of the genital region.43 Tardive bruxism Bruxism, of either the grinding or mixed grinding-clenching type, may develop as a side effect of long-term neuroleptic exposure. It probably represents a forme fruste of tardive oromandibular dystonia.44 A striking feature of the syndrome is noise production, sometimes sufficiently severe to annoy roommates. The movements disappear during sleep. Assessing the severity of tardive syndromes Before prescribing dopamine receptor-blocking drugs, clinicians should strive to document the presence or absence of abnormal involuntary movements. While both physician and nurse-led standardised assessment tools (such as the abnormal involuntary movement scale and ScanMove instrument, respectively) may not always be practical in the busy clinical setting,45 46 a focused examination is nevertheless important. It was recognised over 140 years ago that psychiatric patients may exhibit stereotypies, chorea or abnormal facial grimacing as a result of their disease—failure to document this before treatment may lead to these later being misattributed to a drug effect.47 48 It has also been suggested that some older people develop spontaneous movements of the face as part of normal ageing. Whether this is true or merely represents the emergence of facial or craniocervical dystonic syndromes with age is yet to be resolved. FACTS AND FALLACIES Myth number 1: Second-generation antipsychotics, with their lower D2 binding affinity, have reduced the incidence of tardive syndromes This has been a particularly contentious issue and it is difficult to make a definite statement in either direction. What can be said with certainty is that the introduction of second-generation antipsychotics has not done away with tardive syndromes. Rather, due to rapid uptake in their prescription, including off-label use for mood disorders and sleep, ironically they may have contributed further to the problem. While some studies suggest that the incidence of tardive syndromes with second-generation antipsychotics is not vastly dissimilar from that of their first-generation counterparts,10 49 the largest literature review to date, involving 34, 555 patients treated with antipsychotics across 56 studies, found an annualised incidence rate of 2.98% with second-generation antipsychotics versus 7.7% with first-generation antipsychotics, supporting the claim that second-generation antipsychotics may indeed carry a lower risk.50 A recent large meta-analysis of 57 studies on tardive syndromes also supported this.9 Myth number 2: Prolonged exposure to a causative drug is necessary to be at risk of tardive syndromes Although, as detailed above, the cumulative risk of tardive syndromes increases year-on-year and most patients develop the disorder after at least 1–2 years of drug exposure,23 24 there are reports of its occurrence after just a single dose of neuroleptic. Prolonged drug exposure is therefore not always necessary. Myth number 3: Some neuroleptics are safe The recognition that first-generation (‘typical’) antipsychotics were associated with a number of extrapyramidal side-effects prompted the development of newer compounds, termed ‘atypical’ antipsychotics, which were supposedly defined by the absence of extrapyramidal symptoms at therapeutic doses. Numerous mechanistic differences of these newer compounds, including effects on serotonergic signaling, more rapid dissociation from the D2 receptor, limbic selectivity and in the case of aripiprazole, partial dopaminergic agonism were posited as the reason behind their more favourable side effect profiles. While it is true that not every neuroleptic has the same propensity to cause tardive syndromes, none is devoid of risk. All classes of antipsychotics can produce tardive syndromes.20 51 Nevertheless, newer ‘atypical’ agents probably carry about half the risk of producing later tardive syndromes as compared with their ‘typical’ counterparts.9 Furthermore, it is important to remember that it is not just neuroleptics that are implicated in the development of tardive syndromes (table 1). Differential diagnoses not to miss, and how to spot them Differentiating spontaneous from drug-induced movement disorders in patients with psychiatric illness can be a challenging endeavour. Nonetheless, it is imperative to give adequate thought to excluding important differential diagnoses that can present with the combination of psychiatric disease and abnormal movements,29 and particularly the following conditions: Huntington’s disease As a trinucleotide repeat expansion disorder with the cardinal manifestations of chorea, psychiatric disease and cognitive decline, Huntington’s disease is one of the most important differential diagnoses of tardive dyskinesia. Psychiatric disease (often requiring neuroleptic treatment) can precede the development of hyperkinetic movements in this condition by several years. Inexperienced observers can therefore easily misdiagnose such hyperkinetic movements as tardive. In this setting, there are some particularly helpful clinical clues52 including Hyperkinetic movements: In tardive dyskinesia, these movements tend to be stereotyped and semi-purposeful, as opposed to the random, flowing movements of chorea that typify Huntington’s disease. Topographical distribution: In tardive syndromes, the movements are predominately lower facial and axial, manifesting as retrocollis and opisthotonus. In contrast, patients with Huntington’s disease often have significant limb chorea, which is unusual in tardive syndromes. Hyperkinetic movements of the frontalis muscle are also common in Huntington’s disease but uncommon in tardive syndromes. Eye movements: Eye movement disorders are often a prominent, early feature of Huntington’s disease. They can involve disorders of saccadic initiation, broken pursuits and gaze impersistence. However, in tardive dystonia, the eye movements are generally normal. Thus, a careful oculomotor examination is an important part of the evaluation of all tardive syndromes. Motor impersistence (of grip, tongue protrusion or gaze fixation): This is a classic feature of Huntington’s disease but is very uncommon in tardive dyskinesia, and therefore a valuable clinical sign. Other features: Akathisia and opisthotonus strongly suggest tardive syndromes. Conversely, a family history suggesting dominant inheritance and caudate atrophy on MR scan of brain would suggest Huntington’s disease. Anti-NMDA receptor encephalitis Several autoimmune movement disorders can have co-existent neurobehavioural features, which are extensively reviewed elsewhere.53 Anti-NMDA receptor encephalitis in particular however, could be confused with tardive dyskinesia, due to the prominent stereotyped perioral dyskinesia that typifies the disorder. The condition presents differently depending on age: children have more ‘neurological’ (seizures, movement disorders) phenotypes, while adults tend to present with neurobehavioural syndromes, which can be mistaken for psychosis.54 Sometimes, the neuropsychiatric features require neuroleptic treatment, creating an additional pitfall in the diagnostic pathway. A ‘full house’ of symptoms, including autonomic dysfunction, generally develops within 1 month.54 Clinical suspicion should prompt testing for the causative antibody in serum and cerebrospinal fluid. Wilson’s disease This condition should always be kept in the differential diagnosis of any movement disorder, especially in patients under the age of 40 years (though late presentations are reported). Psychiatric symptoms are common in Wilson’s disease, and perioral movements are also classic. However, they tend to assume a more dystonic quality, frequently producing risus sardonicus. Dysarthria and drooling are also common in Wilson’s disease, but unusual in tardive dyskinesia. Edentulous dyskinesia This hyperkinetic movement disorder affects 15% of the edentulous population,55 manifesting as stereotyped, choreiform perioral and lip movements which bear striking resemblance to tardive oro-bucco-lingual dyskinesia. It presents in people with partial or complete edentulism, and often resolves or significantly improves with the introduction of dentures to the mouth. Its pathogenesis is thought to relate to altered sensory feedback from oral structures as a result of malocclusion. Meige syndrome This primary dystonic disorder mostly affects women in their 50s and 60s, being characterised by the combination of blepharospasm and oromandibular dystonia. Differentiation from tardive conditions on purely clinical grounds can be particularly difficult; hence, a history of exposure to dopamine receptor-blocking agents is critical to explore thoroughly in the history. TREATMENT The management of tardive syndromes should incorporate three key aspects. First, prevention is always better than cure. As such, medications with documented potential for inducing tardive syndromes should be used at the lowest possible dose for the shortest period of time possible. This may of course not always be possible. Second comes the question of medication withdrawal. In actual fact, the evidence that withdrawing the offending drug significantly alters the natural history of tardive syndromes is not as strong as one might think.56 Nevertheless, this is an intuitive move in clinical medicine—remove the thing that is causing the problem. Most movement disorder physicians would therefore advocate stopping the offending dopamine receptor-blocking agent, or at least changing it to a drug with less potential for tardive phenomena, if possible. The alternative drug of choice in this setting is often clozapine, both due to its proven efficacy in the treatment of and its lower risk of inducing tardive syndromes.57–59 Close consultation with psychiatric services is necessary before embarking on such a course of action. It is also important to realise that tardive symptoms may initially worsen following neuroleptic drug withdrawal and that equally the symptoms may be suppressed by switching to a more potent dopamine receptor-blocking agent.60 Finally comes the question of symptomatic treatments for tardive syndromes. Numerous agents have been trialled in this regard, with varying evidence for their effectiveness. As mentioned earlier, tardive syndromes are often a complex medley of different movement disorders, and approaches that may work for one movement may worsen another. It is therefore important to adopt a tailored approach, focused on addressing the issue that primarily bothers the patient; generally, this will be either tardive dyskinesia or tardive dystonia. Concerning tardive dyskinesia, the mainstay of medical treatment resides around the administration of vesicular monoamine transporter-2 (VMAT-2) inhibitors (tetrabenazine, deutetrabenazine, valbenazine—the latter two being the only Food and Drug Administration-approved drugs for the treatment of tardive dystonia), which act through presynaptic dopamine depletion. The main side effects of these medications are the development of reversible parkinsonism, as well as dose-dependent mood changes, particularly in the elderly; the side effect profiles of deutetrabenazine and valbenazine appear significantly more favourable.61 Other compounds worth mentioning include amantadine, which has shown antidyskinetic properties in multiple controlled and uncontrolled studies, and is supported by American Academy of Neurology guidelines for short-term treatment of tardive dyskinesia. Propranolol has surprisingly good data to support its use, though this is likely due to its effect of increasing neuroleptic drug concentrations.47 Clonazepam also appears effective, though in the randomised controlled trial setting it appeared to lose its efficacy after 5–8 months and thus can only be tentatively recommended for short-term use. Several antioxidants have also been trialled but data on their efficacy are largely inconclusive.60 Other options such as additional dopaminergic blockade, for example, with haloperidol, have proven efficacy in reducing tardive dyskinesia, at least in the short term. However, this comes at the cost of an increase in akinetic rigid syndromes. Furthermore, there are insufficient data on the long-term effects of such approaches, and given that these agents have great propensity to cause tardive syndromes, additional potent dopaminergic blockade is not recommended as a treatment for these conditions.60 Botulinum toxin is an effective option for tardive dystonia.23 Trihexyphenidyl can also improve dystonic syndromes, though occasionally at the cost of worsening dyskinesia. Functional neurosurgery is gaining increasing recognition as a treatment for both tardive dyskinesia and dystonia. Indeed, pallidal deep-brain stimulation can be greatly beneficial, and early referral to a centre with experience in this procedure should be encouraged in refractory or debilitating cases.62 Physicians may be reluctant to recommend this procedure due to the risk of worsening underlying psychiatric comorbidity, though in practice, this is seldom an issue, especially with pallidal targets.62 Pallidotomy can also be considered in poor surgical candidates. Tardive akathisia can be equally bothersome, but there is little evidence regarding its optimal treatment. Clonidine, moclobemide and benzodiazepines as well as electroconvulsive therapy have been used in some instances, with varying degrees of success.63–66 Tardive pain syndromes often respond to VMAT-2 inhibitors, though other options such as electroconvulsive therapy have been used.43 Withdrawal emergent dyskinesia often settles spontaneously over a few weeks without treatment. Severe symptoms can however be managed by reintroduction of the offending drug, followed by a slower taper. PATIENT OUTCOMES In an ideal world, patients developing tardive syndromes would have their causative neuroleptic treatment stopped. Then, and only then, could the true reversibility of the syndrome be assessed. However, the nature of psychiatric disease means that ongoing treatment is often needed, making it difficult to assess the outcomes of tardive syndromes. Predictors of poor outcome appear similar to those of developing tardive syndromes in the first place and include advanced age, longer duration of antipsychotic treatment and greater cumulative dose.67 Once established, the severity of tardive syndromes often fluctuates over time, though in a significant proportion, the tardive syndrome fails to resolve.56 68 Key points Tardive syndromes can comprise many characteristic movement disorders; each needs to be carefully sought in suspected cases Clozapine is the drug of choice for patients with tardive syndromes who require ongoing neuroleptic treatment Vesicular monoamine transporter-2 (VMAT-2) inhibitors, such as tetrabenazine, deutetrabenazine and valbenazine, are the best medical treatment options for tardive dyskinesia Pallidal deep-brain stimulation is an effective treatment option in refractory or debilitating tardive syndromes REFERENCES ↵Faurbye A, Rasch P-J, Petersen PB, et al. 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Respiratory dyskinesia. Chest 1994;105:1826–32. doi: 10.1378/chest.105.6.1826OpenUrlCrossRefPubMed ↵Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus). CNS Drugs 2002;16:165–74. doi: 10.2165/00023210-200216030-00003OpenUrlCrossRefPubMed ↵Mejia NI, Jankovic J. Tardive dyskinesia and withdrawal emergent syndrome in children. Expert Rev Neurother 2010;10:893–901. doi: 10.1586/ern.10.58 ↵Sachdev P. Tardive and chronically recurrent oculogyric crises. Mov Disord 1993;8:93–7. doi: 10.1002/mds.870080117OpenUrlCrossRefPubMed ↵FitzGerald PM, Jankovic J. Tardive oculogyric crises. Neurology 1989;39:1434–1434. doi: 10.1212/WNL.39.11.1434OpenUrl ↵Ford B, Greene P, Fahn S. Oral and genital tardive pain syndromes. Neurology 1994;44:2115–2115. doi: 10.1212/WNL.44.11.2115OpenUrl ↵Micheli F, Pardal MF, Gatto M, et al. Bruxism secondary to chronic antidopaminergic drug exposure. 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Br J Psychiatry 2012;200:387–92. doi: 10.1192/bjp.bp.111.101485 ↵Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry 2008;21:151–6. doi: 10.1097/YCO.0b013e3282f53132 ↵Ertugrul A, Demir B. Clozapine-induced tardive dyskinesia: a case report. Prog Neuro-Psychopharmacology Biol Psychiatry 2005;29:633–5. doi: 10.1016/j.pnpbp.2005.01.014OpenUrl ↵Kumar H, Jog M. Missing Huntington’s disease for tardive dyskinesia: a preventable error. Can J Neurol Sci/J Can Des Sci Neurol 2011;38:762–4. doi: 10.1017/S0317167100012294OpenUrl ↵Balint B, Vincent A, Meinck H-M, et al. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain 2018;141:13–36. doi: 10.1093/brain/awx189OpenUrlCrossRefPubMed ↵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. 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Josep Dalmau receives the “Scientific Breakthrough 2023” Award from the American Brain Foundation

From www.clinicbarcelona.org - May 23, 2023 2:38 PM
The accolade recognises the commitment of this Clínic Barcelona-IDIBAPS researcher to deepening our understanding of autoimmune neurological diseases such...
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IDIBAPS creates three multidisciplinary research programs to encourage collaboration among its groups

From www.clinicbarcelona.org - September 5, 2023 11:21 AM
They are the Translational cancer research program, the Synaptic autoimmunity in neurology, psychiatry and cognitive neuroscience program and the Lymphoid...
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ExTINGUISH: A Beacon of Hope for NMDAR Encephalitis

From youtu.be - August 6, 2023 7:10 PM
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MR Imaging Findings in a Large Population of Autoimmune Encephalitis | American Journal of Neuroradiology

MR Imaging Findings in a Large Population of Autoimmune Encephalitis | American Journal of Neuroradiology | AntiNMDA | Scoop.it
From www.ajnr.org - July 27, 2023 11:18 AM
Research ArticleAdult Brain MR Imaging Findings in a Large Population of Autoimmune Encephalitis S. Gillon, M. Chan, J. Chen, E.L. Guterman, X. Wu, C.M. Glastonbury and Y. Li American Journal of Neuroradiology July 2023, 44 (7) 799-806; DOI: https://doi.org/10.3174/ajnr.A7907 ArticleFigures & DataInfo & MetricsReferences PDF This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased. AbstractBACKGROUND AND PURPOSE: Autoimmune encephalitis is a rare condition in which autoantibodies attack neuronal tissue, causing neuropsychiatric disturbances. This study sought to evaluate MR imaging findings associated with subtypes and categories of autoimmune encephalitis.MATERIALS AND METHODS: Cases of autoimmune encephalitis with specific autoantibodies were identified from the medical record (2009–2019). Cases were excluded if no MR imaging of the brain was available, antibodies were associated with demyelinating disease, or >1 concurrent antibody was present. Demographics, CSF profile, antibody subtype and group (group 1 intracellular antigen or group 2 extracellular antigen), and MR imaging features at symptom onset were reviewed. Imaging and clinical features were compared across antibody groups using χ2 and Wilcoxon rank-sum tests.RESULTS: Eighty-five cases of autoimmune encephalitis constituting 16 distinct antibodies were reviewed. The most common antibodies were anti-N-methyl-D-aspartate (n = 41), anti-glutamic acid decarboxylase (n = 7), and anti-voltage-gated potassium channel (n = 6). Eighteen of 85 (21%) were group 1; and 67/85 (79%) were group 2. The median time between MR imaging and antibody diagnosis was 14 days (interquartile range, 4–26 days). MR imaging had normal findings in 33/85 (39%), and 20/33 (61%) patients with normal MRIs had anti-N-methyl-D-aspartate receptor antibodies. Signal abnormality was most common in the limbic system (28/85, 33%); 1/68 (1.5%) had susceptibility artifacts. Brainstem and cerebellar involvement were more common in group 1, while leptomeningeal enhancement was more common in group 2.CONCLUSIONS: Sixty-one percent of patients with autoimmune encephalitis had abnormal brain MR imaging findings at symptom onset, most commonly involving the limbic system. Susceptibility artifact is rare and makes autoimmune encephalitis less likely as a diagnosis. Brainstem and cerebellar involvement were more common in group 1, while leptomeningeal enhancement was more common in group 2.ABBREVIATIONS:AIEautoimmune encephalitisanti-Gq1banti-ganglioside Q1banti-LGI1anti-leucine-rich glioma inactivated 1CASPR2contactin-associated protein-like 2GABAgamma-aminobutyric acidGADglutamic acid decarboxylaseGFAPglial fibrillary acidic proteinNMDAN-methyl-D-aspartatePD-1programmed cell death protein 1VGCCvoltage gated calcium channelVGKCvoltage-gated potassium channel© 2023 by American Journal of NeuroradiologyView Full Text Log in using your username and password Username * Password * Forgot your user name or password? PreviousNext Back to top In this issue American Journal of Neuroradiology Vol. 44, Issue 7 1 Jul 2023 Table of ContentsIndex by authorComplete Issue (PDF) Print Download PDF Email Article Citation Tools Share Tweet WidgetFacebook LikeGoogle Plus One Purchase Related ArticlesNo related articles found.PubMedGoogle Scholar Cited By...No citing articles found.CrossrefGoogle Scholar More in this TOC Section Cost-Effectiveness Analysis of 68Ga-DOTATATE PET/MRI in Radiotherapy Planning in Patients with Intermediate-Risk Meningioma Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study Show more ADULT BRAIN Similar Articles
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Elevated blood and cerebrospinal fluid biomarkers of microglial activation and blood‒brain barrier disruption in anti-NMDA receptor encephalitis | Journal of Neuroinflammation | Full Text

Elevated blood and cerebrospinal fluid biomarkers of microglial activation and blood‒brain barrier disruption in anti-NMDA receptor encephalitis | Journal of Neuroinflammation | Full Text | AntiNMDA | Scoop.it
From jneuroinflammation.biomedcentral.com - July 27, 2023 11:01 AM
Background Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the...
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Anti-N-methyl-d-aspartate receptor encephalitis and positive human herpesvirus-7 deoxyribonucleic acid in cerebrospinal fluid: a case report | Journal of Medical Case Reports | Full Text

Anti-N-methyl-d-aspartate receptor encephalitis and positive human herpesvirus-7 deoxyribonucleic acid in cerebrospinal fluid: a case report | Journal of Medical Case Reports | Full Text | AntiNMDA | Scoop.it
From jmedicalcasereports.biomedcentral.com - July 14, 2023 2:17 PM
Background Anti-N-methyl-d-aspartate receptor encephalitis is a neuroautoimmune syndrome typically presenting with seizures, psychiatric symptoms, and autonomic dysfunction. Human herpesvirus-7 is often found with human herpesvirus-6 and infects leukocytes such as T-cells, monocytes–macrophages,...
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We have a winner! - The Anti-NMDA Receptor Encephalitis Foundation Prize, 2023

We have a winner! - The Anti-NMDA Receptor Encephalitis Foundation Prize, 2023 | AntiNMDA | Scoop.it
From www.antinmdafoundation.org - June 25, 2023 2:58 PM
It’s that time of year again, when the Foundation is delighted to offer its annual Anti-NMDA Receptor Encephalitis Foundation Prize to a promising neurology trainee ...Read More...
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Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia | Neurology Neuroimmunology & Neuroinflammation

Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
From nn.neurology.org - June 19, 2023 9:45 PM
AbstractBackground & Objectives Autoimmune encephalitis (AIE) may present with prominent cognitive disturbances without overt inflammatory changes in MRI and CSF. Identification of these neurodegenerative dementia diagnosis mimics is important because patients generally respond to immunotherapy. The objective of this study was to determine the frequency of neuronal antibodies in patients with presumed neurodegenerative dementia and describe the clinical characteristics of the patients with neuronal antibodies.Methods In this retrospective cohort study, 920 patients were included with neurodegenerative dementia diagnosis from established cohorts at 2 large Dutch academic memory clinics. In total, 1,398 samples were tested (both CSF and serum in 478 patients) using immunohistochemistry (IHC), cell-based assays (CBA), and live hippocampal cell cultures (LN). To ascertain specificity and prevent false positive results, samples had to test positive by at least 2 different research techniques. Clinical data were retrieved from patient files.Results Neuronal antibodies were detected in 7 patients (0.8%), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX, and anti-NMDAR. Clinical symptoms atypical for neurodegenerative diseases were identified in all 7 and included subacute deterioration (n = 3), myoclonus (n = 2), a history of autoimmune disease (n = 2), a fluctuating disease course (n = 1), and epileptic seizures (n = 1). In this cohort, no patients with antibodies fulfilled the criteria for rapidly progressive dementia (RPD), yet a subacute deterioration was reported in 3 patients later in the disease course. Brain MRI of none of the patients demonstrated abnormalities suggestive for AIE. CSF pleocytosis was found in 1 patient, considered as an atypical sign for neurodegenerative diseases. Compared with patients without neuronal antibodies (4 per antibody-positive patient), atypical clinical signs for neurodegenerative diseases were seen more frequently among the patients with antibodies (100% vs 21%, p = 0.0003), especially a subacute deterioration or fluctuating course (57% vs 7%, p = 0.009).Discussion A small, but clinically relevant proportion of patients suspected to have neurodegenerative dementias have neuronal antibodies indicative of AIE and might benefit from immunotherapy. In patients with atypical signs for neurodegenerative diseases, clinicians should consider neuronal antibody testing. Physicians should keep in mind the clinical phenotype and confirmation of positive test results to avoid false positive results and administration of potential harmful therapy for the wrong indication.GlossaryAD=Alzheimer dementia; AIE=autoimmune encephalitis; CBA=cell-based assays; DLB=dementia with Lewy bodies; IHC=immunohistochemistry; LN=live hippocampal cell cultures; PPA=primary progressive aphasia; PSP=progressive supranuclear palsy; RPD=rapidly progressive dementia; VGCC=voltage-gated calcium channelCognitive dysfunction can be the presenting and most prominent symptom in patients with autoimmune encephalitis (AIE).1,2 In contrast to neurodegenerative diseases, patients with antibody-mediated encephalitis might benefit from immunotherapy and improve considerably.3,4 The presence of neuronal antibodies has been reported predominantly in rapidly progressive dementia (RPD).5,6 However, AIE can present less fulminantly and is therefore potentially missed, resulting in diagnosis and treatment delay or even misdiagnosis.7,8 We hypothesized that a small—but not insignificant—part of dementia syndromes is indeed caused by antibody-mediated encephalitis and underdiagnosed, withholding these patients' available treatments. The wish to diagnose every single patient with autoimmune encephalitis is in opposition with the risk for false positive tests.9 Therefore, we strictly adhere to confirmation of positive test results with 2 different test techniques. In this study, we describe the frequency of neuronal antibodies in a cohort of patients diagnosed with various dementia syndromes in a memory clinic. In addition, we present clues to improve clinical recognition of AIE in dementia syndromes.MethodsPatients and Laboratory StudiesIn this retrospective multicenter study, we tested for the presence of neuronal antibodies in serum and CSF samples from patients diagnosed with neurodegenerative dementia diagnosis, included earlier prospectively in established cohorts at 2 large Dutch academic memory clinics (Erasmus University Medical Center, Amsterdam University Medical Centers, location VUmc)10 between 1998 and 2016 (84% last 10 years). All patients fulfilled the core clinical criteria for dementia, as defined by the National Institutes of Aging-Alzheimer Association workgroups.11 Patients were classified into 4 subgroups (based on diagnostic criteria): Alzheimer dementia (AD), frontotemporal dementia (FTD; both behavioral variant and primary progressive aphasia [PPA]), dementia with Lewy bodies (DLB), and other dementia syndromes.11,-,14 Rapidly progressive dementia was defined as dementia within 12 months or death within 2 years after the appearance of the first cognitive symptoms.15 Patients with vascular dementia were not included. Clinic information was retrieved from the prospectively collected data. A subacute deterioration was defined as a marked progression of symptoms in 3 months and a fluctuating course as a disease course fluctuating over a longer period (e.g., weeks to months; different from the fluctuations within a day as seen in some patients with DLB). Dementia markers were scored according to the reference values (per year and per center; included in Table 1).View inline View popup Table 1 Patient Characteristics of Auto-antibody Positive PatientsAll samples, stored in both cohorts' biobanks, were screened for immunoreactivity with immunohistochemistry (IHC), as previously described.16 Preferably, paired serum and CSF were tested for optimal sensitivity and specificity. Samples that were showing a positive or questionable staining pattern were tested more extensively using validated commercial cell-based assays (CBA) and in-house CBA (eTable 1, links.lww.com/NXI/A869). In addition, these samples were tested with live hippocampal cell cultures (LN).16,17 To ascertain specificity, only samples that could be confirmed by CBA or LN were scored as positive because there is a higher risk for false-positive test results in this population with a low a priori chance to have encephalitis.9,18 If IHC was suggestive for antibodies against intracellular (paraneoplastic) targets, this was explored by a different IHC technique.19 Anti-thyroid peroxidase (TPO), voltage-gated calcium channel (VGCC), or low titer glutamic acid decarboxylase antibodies were not tested for because these are generally nonspecific at these ages and are not associated with dementia syndromes.Antibody-positive patients were described exploratory and compared with a randomly selected antibody-negative group (ratio 1:4) matched for memory clinic, dementia subtype, sex, and age (±5 years). For these comparisons, medical records were additionally assessed for both the antibody-positive and antibody-negative patients. All antibody-positive patients were reviewed by a panel consisting of neurologists specialized in neurodegenerative (F.J., H.S., J.S.) or autoimmune diseases (J.V., P.S.S., M.T.), and a consensus classification of AIE vs AIE with a neurodegenerative dementia comorbidity was reached.Statistical AnalysisWe used IBM SPSS 25.0 (SPSS Inc) and Prism 8.4.3 (GraphPad) for statistical analysis. Baseline characteristics were analyzed using the Fisher exact test, the Fisher-Freeman-Halton test, or the Kruskal-Wallis test, when appropriate. For group comparisons, encompassing categorical data, we used the Pearson χ2 test or the Fisher-Freeman-Halton test, when appropriate. Continuous data were analyzed using the Mann-Whitney U test. All p-values were two-sided and considered statistically significant when below 0.05. We applied no correction for multiple testing, and therefore, p values between 0.05 and 0.005 should be interpreted carefully.Standard Protocol Approvals, Registrations, and Patient ConsentsThe study was approved by The Institutional Review Boards of Erasmus University Medical Center Rotterdam and Amsterdam University Medical Center, location VUmc. Written informed consent was obtained from all patients.Data AvailabilityAny data not published within this article are available at the Erasmus MC University Medical Center. Patient-related data will be shared on reasonable request from any qualified investigator, maintaining anonymization of the individual patients.ResultsIn total, 1,398 samples from 920 patients were tested (Figure; in 478, both CSF and serum [52%]). Three-hundred fifty-eight patients were classified as AD (39%), 283 FTD (31%), and 161 DLB (17%). The fourth subgroup with other dementia syndromes consisted of 118 patients (13%), including progressive supranuclear palsy (n = 48, 5%) and corticobasal syndrome (n = 29, 3%). The median age at disease onset was 62 years (range 16–90 years). Male patients were overrepresented (n = 542, 59%), and 60 patients (7%) fulfilled the criteria for rapidly progressive dementia (RPD; eTable 2, links.lww.com/NXI/A869).<img class="highwire-fragment fragment-image" alt="Figure" width="440" height="305" src="https://nn.neurology.org/content/nnn/10/5/e200137/F1.medium.gif">Download figure Open in new tab Download powerpoint Figure Flowchart of Patient Inclusion With Antibody ResultsIn total, 920 patients (1,398 samples) with a presumed neurodegenerative dementia syndrome were tested for the presence of neuronal antibodies in serum and CSF. Neuronal antibodies were detected in 7 patients (0.8%, 95% CI 0.2–1.3); five among the 358 Alzheimer disease patients. Subclassification of the ‘other’ group is provided in supplementary table eTable 2 (links.lww.com/NXI/A869). AD = Alzheimer disease; DLB = diffuse Lewy body dementia; DPPX = dipeptidyl aminopeptidase-like protein 6; FTD = frontotemporal dementia; IgLON5 = Ig-like domain-containing protein family member 5; LGI1 = leucin-rich glioma inactivated protein 1; NMDAR = N-methyl-d-aspartate receptor; S = serum.Neuronal antibodies were detected in 7 patients (0.8%; 5 in the AD group: 1.4%; Figure), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX (n = 1), and anti-NMDAR antibodies (n = 1; Table 1). Among these 7, 4 patients were diagnosed retrospectively with an exclusive diagnosis of AIE, while 3 patients were classified to have AIE (anti-IgLON5 [n = 2] and anti-NMDAR antibodies [n = 1]) with a neurodegenerative dementia comorbidity. No patients with antibodies fulfilled the criteria for RPD, yet a subacute deterioration later in the disease was reported in 3 patients. Atypical clinical signs for neurodegenerative diseases were present in 7 of 7 antibody-positive patients (100% vs 21% in antibody-negative patients, p = 0.0003; Table 2). These included a subacute deterioration (n = 3), myoclonus (n = 2), a fluctuating disease course over months (n = 1), a history of autoimmune disease (n = 2), and epileptic seizures (n = 1; Table 1). Brain MRI of none of the patients demonstrated abnormalities suggestive for active AIE, in particular no hippocampal swelling nor increased T2-signal intensity. CSF pleocytosis was found in 1 patient. CSF biomarkers (t-tau, p-tau, and Aβ42) were tested in 5 of 7 patients, and t-tau and p-tau were increased in 4, while a low Aβ42 was seen in 2. Of note, only 1 patient had the combination of reduced Aβ42 and increased p-tau/t-tau, and was diagnosed with a comorbid AD. No patient received immunotherapy. Two patients still alive (1 anti-LG1, 1 anti-DPPX positive) were contacted but refused to visit our clinic to try very delayed immunotherapy trials. It is of interest that the patient with anti-DPPX antibodies showed spontaneous improvement of cognitive disturbances, atypical for a pure neurodegenerative disease.View inline View popup Table 2 Comparisons Between Patients With Neuronal Auto-antibodies and Antibody-Negative PatientsCompared with the patients without neuronal antibodies, subacute cognitive deterioration or fluctuating course was present more frequently (4/7 [57%] vs 2/28 [7%], p = 0.009). Although movement disorders (myoclonus) and autoimmune disorders were present in 2 of 7 patients each, this did not reach significance (Table 2).DiscussionIn this large, multicenter, cohort study consisting of patients with a presumed neurodegenerative dementia diagnosis, we show that a small, but clinically relevant proportion (0.8%) have neuronal antibodies. In this particular group, 4 of 7 antibody-positive patients presented with an atypical clinical course (subacute deterioration or fluctuating disease course), which is considered as a clinical clue (‘red flag’) for an antibody-mediated etiology of dementia.4 It is important that a fluctuating disease course was observed over a longer period (e.g., weeks or months) in AIE and should not be confused with shorter fluctuations of cognition or alertness (over the day) in DLB. Other known red flags, which we observed in these 7 patients, were myoclonus, epilepsy, pleocytosis, or a history of autoimmune disorders, as described earlier.1,4,-,6 Compared with antibody-negative patients, no significant difference was found related to these symptoms alone, probably due to the low number of positive patients and related low power. However, atypical clinical signs for neurodegenerative diseases together were seen significantly more frequently in the antibody-positive group. Within this cohort mostly devoid of patients with RPD, none of the antibody-positive patients fulfilled the criteria for RPD, nor ancillary testing showed specific signs for AIE in most patients. This implicates that AIE can resemble more protracted, progressive neurodegenerative dementia syndromes, as we reported earlier.1Three antibody-positive patients had IgLON5 antibodies, which is a very rare and known to have heterogeneous (chronic) clinical manifestations, including pronounced sleep problems, cognitive dysfunction, and movement disorders.20,21 Misdiagnosis with progressive supranuclear palsy (PSP) is reported, mainly associated with the preceding movement disorders. In addition, half of the patients have cognitive impairment of whom 20% fulfilled clinical criteria for dementia.21 It is of interest that IgLON5 disease shares features with neurodegeneration because autopsy studies showed tau deposits.22 However, there is a strong HLA association,20 and studies show that antibodies directly bind to surface IgLON5 on neurons and directly alter neuronal function and structure,23 suggesting a primary inflammatory disease.In previous research, a notably higher frequency (14%) of neuronal antibodies in patients with dementia was reported by Giannocaro et al.24 The discrepancy with our test results is probably explained by differences in patient selection and antibody testing methodology. First, 30% of the patients in the cohort described by Giannocaro et al. demonstrated CSF inflammatory abnormalities, indicating a relatively high pretest probability of antibody-positivity compared with our study.24 A lack of CSF pleocytosis probably better represents the population of memory clinics. Second, the previous study exclusively tested serum by cell-based assay without confirmatory tests nor testing antibodies in CSF.24 We only considered antibody test results positive when confirmed by additional techniques to avoid suboptimal specificity and false-positive test results.9Previous studies, including our own, suggested RPD as a relevant red flag for AIE,1,4,9,25 but we cannot determine this from our study based on the design of our study. We included patients at tertiary memory clinics without overt signs or symptoms suggestive for encephalitis. Therefore, the amount of patients with RPD included was very limited (7%), comparable with other large dementia cohort studies, as was the amount of patients with abnormal ancillary testing suggestive for AIE because this would have prompted a different approach than referral to a tertiary memory clinic. These patients with RPD and ancillary testing suggestive of AIE were not included in our study. Inclusion of those patients would have likely increased our rate of positivity.The strength of our study is the large number of paired samples (serum and CSF combined) from a cohort with various presumed neurodegenerative diseases without AIE suspicion, representative for academic memory clinics. A limitation is the lack of neuropathologic data to support our findings and make diagnoses of neurodegeneration or inflammation definite. To confirm if the symptoms are related to the presence of antibodies, we tried to overcome this concern in different ways. First, the presence of antibodies in serum and CSF was confirmed by different techniques (cell-based assay, tissue immunohistochemistry, and cultured live neurons), indicating optimal test specificity. Second, afterward patients were thoroughly reviewed by a panel of neurologists specialized in neurodegenerative or autoimmune disease to detect atypical signs and symptoms related to AIE. This is a very large cohort of patients with dementia examined for the presence of neuronal antibodies. Nevertheless, an important limitation of this study is the small number of antibody-positive patients, underpowering the probability to identify significant differences between antibody-positive and antibody-negative patients. The low number of patients with RPD has probably added to this small number, and a prospective study including patients with RPD is recommended. Nevertheless, several probable red flags could be identified. Diagnosing AIE in patients with dementia is highly relevant because these patients might respond to immunotherapy. Therefore, clinicians should test for neuronal antibody in patients demonstrating red flags suggestive for an autoimmune etiology, if possible early in disease course. When profound temporal lobe atrophy already has developed, little effect is to be expected. Red flags identified in this study are subacute deterioration or fluctuating course. Other red flags described previously, we also see reflected in our study, are autoimmune disorders, myoclonus, seizures, and pleocytosis,1,4,-,6 Preferably, both serum and CSF should be tested and confirmed by additional techniques. Always consider the possibility of a false positive test result, especially when only using a single technique (like the commercial cell-based assay). If the clinical phenotype is atypical, confirmation in a research laboratory should be mandatory. The use of antibody panels is discouraged, especially including the paraneoplastic blots, because these are associated with higher risks of lack of clinical relevance.26 This caution is even more warranted for tests not associated with neurodegenerative syndromes, but with a history of nonspecificity, including VGKC (in the absence of LGI1 or CASPR2), VGCC, anti-TPO, and low-titer anti-GAD65.27,-,30 Further research should focus on improving clinical recognition of AIE in patients with dementia determining the effect of immunotherapy in this specific patient category and assessing the frequency of AIE in RPD.In conclusion, we have shown that a clinically relevant, albeit small proportion of patients with a suspected neurodegenerative disease and nonrapidly progressive course have neuronal antibodies indicative of AIE.Study FundingM.J. Titulaer was supported by an Erasmus MC fellowship and has received funding from the Netherlands Organization for Scientific Research (NWO, Veni incentive), ZonMw (Memorabel program), the Dutch Epilepsy Foundation (NEF 14-19 & 19-08), Dioraphte (2001 0403), and E-RARE JTC 2018 (UltraAIE, 90030376505). F. Leypoldt has received funding from the German Ministry of Education and Research (01GM1908A) and the Era-Net funding program (LE3064/2-1).DisclosureA.E.M. Bastiaansen reports no disclosures. R.W. van Steenhoven reports no disclosures. Research programs of Wiesje van der Flier have been funded by ZonMW, now, EUFP7, EU-JPND, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, and Combinostics. W.M. van der Flier holds the Pasman chair. W.M. van der Flier is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). All funding is paid to her institution. WF has performed contract research for Biogen MA Inc and Boehringer Ingelheim. All funding is paid to her institution. W.M. van der Flier has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), and Springer Healthcare. All funding is paid to her institution. W.M. van der Flier is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. All funding is paid to her institution. W.M. van der Flier participated in advisory boards of Biogen MA Inc and Roche. All funding is paid to her institution. W.M. van der Flier is a member of the steering committee of PAVE and Think Brain Health. W.M. van der Flier was an associate editor of Alzheimer, Research & Therapy in 2020/2021. W.M. van der Flier is an associate editor at Brain. Research of C. Teunissen was supported by the European Commission (Marie Curie International Training Network, Grant Agreement No. 860197 (MIRIADE)), Innovative Medicines Initiatives 3TR (Horizon 2020, Grant No. 831434), EPND (IMI 2 Joint Undertaking (JU) under Grant Agreement No. 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance) and Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, and Alzheimer Association. C. Teunissen is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP-allowance, #LSHM20106). ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. C. Teunissen has a collaboration contract with ADx Neurosciences, Quanterix, and Eli Lilly, performed contract research or received grants from AC-Immune, Axon Neurosciences, Bioconnect, Bioorchestra, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, Grifols, Novo Nordisk, PeopleBio, Roche, Toyama, and Vivoryon. She serves on editorial boards of Medidact Neurologie/Springer, Alzheimer Research and Therapy, and Neurology: Neuroimmunology & Neuroinflammation and is an editor of a Neuromethods book Springer. She had speaker contracts for Roche, Grifols, and Novo Nordisk. E. de Graaff holds a patent for the detection of anti-DNER antibodies. M.M.P. Nagtzaam reports no disclosures. M. Paunovic reports no disclosures. S. Franken reports no disclosures. M.W.J. Schreurs reports no disclosures. F. Leypoldt has received speakers honoraria from Grifols, Roche, Novartis, Alexion, and Biogen and serves on an advisory board for Roche and Biogen. He works for an academic institution (University Hospital Schleswig-Holstein) which offers commercial autoantibody testing. P.A.E. Sillevis Smitt holds a patent for the detection of anti-DNER and received research support from Euroimmun. J.M. de Vries reports no disclosures. H. Seelaar reports no disclosures. J.C. van Swieten reports no disclosures. F.J. de Jong reports no disclosures. Y.A.L. Pijnenburg Research of Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The chair of Wiesje van der Flier is supported by the Pasman stichting. M.J. Titulaer has filed a patent, on behalf of the Erasmus MC, for methods for typing neurologic disorders and cancer, and devices for use therein, and has received research funds for serving on a scientific advisory board of Horizon Therapeutics, for consultation at Guidepoint Global LLC, for consultation at UCB, for teaching colleagues by Novartis. MT has received an unrestricted research grant from Euroimmun AG and from CSL Behring. Go to Neurology.org/NN for full disclosure.AcknowledgmentThe authors thank all patients for their participation. The authors also thank Esther Hulsenboom and Ashraf Jozefzoon-Aghai for their technical assistance. M.W.J. Schreurs, F. Leypoldt, P.A.E. Sillevis Smitt, J.M. de Vries, and M.J. Titulaer of this publication are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory, and Autoimmune Diseases—Project ID No. 739543 (ERN-RITA; HCP Erasmus MC and University Hospital Schleswig-Holstein). H. Seelaar, J.C. van Swieten, and F.J. de Jong of this publication are members of the European Reference Network for Rare Neurological Diseases—Project ID 73910. Research of the VUmc Alzheimer center is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center VUmc is supported by Alzheimer Nederland and Stichting VUmc Fonds. The clinical database structure was developed with funding from Stichting Dioraphte.Appendix Authors<img class="highwire-fragment fragment-image" alt="Table" src="https://nn.neurology.org/content/nnn/10/5/e200137/T3.medium.gif"; width="599" height="2531">FootnotesGo to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.The Article Processing Charge was funded the authors.Submitted and externally peer reviewed. The handling editor was Editor Josep O. Dalmau, MD, PhD, FAAN.Received December 8, 2022.Accepted in final form May 8, 2023.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.References1.↵Bastiaansen AEM, van Steenhoven RW, de Bruijn M, et al. Autoimmune encephalitis resembling dementia syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1039.OpenUrlAbstract/FREE Full Text2.↵Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol. 2010;9(1):67-76.OpenUrlCrossRefPubMed3.↵Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12(2):157-165.OpenUrlCrossRefPubMed4.↵Flanagan EP, McKeon A, Lennon VA, et al. Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc. 2010;85(10):881-897.OpenUrlCrossRefPubMed5.↵Geschwind MD, Tan KM, Lennon VA, et al. Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease. Arch Neurol. 2008;65(10):1341-1346.OpenUrlCrossRefPubMed6.↵Grau-Rivera O, Sanchez-Valle R, Saiz A, et al. Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease. JAMA Neurol. 2014;71(1):74-78.OpenUrl7.↵Titulaer MJ, McCracken L, Gabilondo I, et al. Late-onset anti-NMDA receptor encephalitis. Neurology. 2013;81(12):1058-1063.OpenUrlAbstract/FREE Full Text8.↵Gaig C, Graus F, Compta Y, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology. 2017;88(18):1736-1743.OpenUrlAbstract/FREE Full Text9.↵Bastiaansen AEM, de Bruijn M, Schuller SL, et al. Anti-NMDAR encephalitis in The Netherlands, focusing on late-onset patients and antibody test accuracy. Neurol Neuroimmunol Neuroinflamm. 2022;9(2):e1127.OpenUrl10.↵van der Flier WM, Scheltens P. Amsterdam dementia cohort: performing research to optimize care. J Alzheimers Dis. 2018;62(3):1091-1111.OpenUrl11.↵McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-269.OpenUrlCrossRefPubMed12.↵Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456-2477.OpenUrlCrossRefPubMed13.↵Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014.OpenUrlAbstract/FREE Full Text14.↵McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88-100.OpenUrlAbstract/FREE Full Text15.↵Geschwind MD. Rapidly progressive dementia. Continuum (Minneap Minn). 2016;22(2 Dementia):510-537.OpenUrl16.↵Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 2005;128(Pt 8):1764-1777.OpenUrlCrossRefPubMed17.↵Gresa-Arribas N, Titulaer MJ, Torrents A, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13(2):167-177.OpenUrlCrossRefPubMed18.↵Martinez-Martinez P, Titulaer MJ. Autoimmune psychosis. Lancet Psychiatry. 2020;7(2):122-123.OpenUrl19.↵van Coevorden-Hameete MH, Titulaer MJ, Schreurs MW, et al. Detection and characterization of autoantibodies to neuronal cell-surface antigens in the central nervous system. Front Mol Neurosci. 2016;9:37.OpenUrl20.↵Sabater L, Gaig C, Gelpi E, et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol. 2014;13(6):575-586.OpenUrlCrossRefPubMed21.↵Gaig C, Compta Y, Heidbreder A, et al. Frequency and characterization of movement disorders in anti-IgLON5 disease. Neurology. 2021;97(14):e1367–e1381.OpenUrlAbstract/FREE Full Text22.↵Gelpi E, Hoftberger R, Graus F, et al. Neuropathological criteria of anti-IgLON5-related tauopathy. Acta Neuropathol. 2016;132(4):531-543.OpenUrlCrossRefPubMed23.↵Landa J, Gaig C, Plaguma J, et al. Effects of IgLON5 antibodies on neuronal cytoskeleton: a link between autoimmunity and neurodegeneration. Ann Neurol. 2020;88(5):1023-1027.OpenUrlCrossRefPubMed24.↵Giannoccaro MP, Gastaldi M, Rizzo G, et al. Antibodies to neuronal surface antigens in patients with a clinical diagnosis of neurodegenerative disorder. Brain Behav Immun. 2021;96:106-112.OpenUrl25.↵Hermann P, Zerr I. Rapidly progressive dementias - aetiologies, diagnosis and management. Nat Rev Neurol. 2022;18(6):363-376.OpenUrl26.↵Dechelotte B, Muniz-Castrillo S, Joubert B, et al. Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e701.OpenUrlAbstract/FREE Full Text27.↵van Sonderen A, Schreurs MW, de Bruijn MA, et al. The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology. 2016;86(18):1692-1699.OpenUrlCrossRefPubMed28.↵Muñoz Lopetegi A, Boukhrissi S, Bastiaansen A, et al. Neurological syndromes related to anti-GAD65: clinical and serological response to treatment. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e696.OpenUrlAbstract/FREE Full Text29.↵Mattozzi S, Sabater L, Escudero D, et al. Hashimoto encephalopathy in the 21st century. Neurology. 2020;94(2):e217-e224.OpenUrlAbstract/FREE Full Text30.↵Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80(1):30-39.OpenUrl
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Research study - can you help?

Research study - can you help? | AntiNMDA | Scoop.it
From www.encephalitis.info - June 19, 2023 9:38 PM
Researchers at Kings College London are looking for young people to travel to London and help with an encephalitis study...
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Sociocultural Influences in Autoimmune Encephalitis Without Neurologic Symptoms

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

Anti N-Methyl-D-Aspartate receptor antibody associated Acute Demyelinating Encephalomyelitis in a patient with COVID-19: a case report | Journal of Medical Case Reports | Full Text | AntiNMDA | Scoop.it
From jmedicalcasereports.biomedcentral.com - June 19, 2023 9:27 PM
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Autoimmune Encephalitis Consensus Criteria | Neurology Clinical Practice

Autoimmune Encephalitis Consensus Criteria | Neurology Clinical Practice | AntiNMDA | Scoop.it
From cp.neurology.org - June 14, 2023 7:42 PM
June 2023; 13 (3) Editorial Autoimmune Encephalitis Consensus CriteriaLessons Learned From Real-World Practice View ORCID ProfileJeffrey M. Gelfand, Chu-Yueh Guo First published April 25, 2023, DOI: https://doi.org/10.1212/CPJ.0000000000200155 Full PDF Citation Permissions Make Comment See Comments Downloads133 Share Article Info & Disclosures This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased. Autoimmune encephalitis (AE) encompasses a spectrum of neurologic disorders caused by brain inflammation, a subset of which is associated with autoantibodies to neuronal cell-surface antigens such as anti-N-methyl-d-aspartate (NMDA) receptor AE or anti-leucine-rich glioma-inactivated 1 (LGI1) AE.1 Up to half of patients with AE, however, do not have abnormal neuronal or glial autoantibodies identified and are classified as having “seronegative” AE.2 Clinical antibody testing can take several days to result, a time in which clinicians caring for patients with suspected AE may wish to initiate empiric immunosuppressive therapy. Antibody testing is also not readily accessible in some health care settings and, even when technically available, may require time-consuming advocacy with local clinical laboratories to justify relatively costly send-out testing. To add further complexity, some patients with immunoreactive (e.g., laboratory true-positive) antibodies do not have clinical AE, and over-reliance and misapplication of antibody testing were identified as important contributors to AE misdiagnosis in a 2023 multicenter analysis.3FootnotesFunding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.See page e200151© 2023 American Academy of NeurologyView Full Text AAN Members We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page. Google Safari Microsoft Edge Firefox Click here to login AAN Non-Member Subscribers Click here to login Purchase access For assistance, please contact: AAN Members (800) 879-1960 or (612) 928-6000 (International) Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international) Sign Up Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here Purchase Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed. You May Also be Interested in Back to top Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials Dr. Nicole Sur and Dr. Mausaminben Hathidara ► Watch Related Articles Autoimmune Encephalitis Criteria in Clinical Practice Topics Discussed All Clinical Neurology Autoimmune diseases Encephalitis Alert Me Alert me when eletters are published
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Predictive Value of Serum Neurofilament Light Chain Levels in Anti-NMDA Receptor Encephalitis

Predictive Value of Serum Neurofilament Light Chain Levels in Anti-NMDA Receptor Encephalitis | AntiNMDA | Scoop.it
From pubmed.ncbi.nlm.nih.gov - June 14, 2023 7:41 PM
Increased serum NfL levels reflect neuroaxonal damage in anti-NMDAR encephalitis. No relationship was identified with disease severity, whereas the association with outcome was confounded by age.The implied role of sampling timing on NfL levels also limits the applicability of NfL as a prognostic...
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Frontiers | The MOG antibody associated encephalitis preceded by COVID-19 infection; a case study and systematic review of the literature

Frontiers | The MOG antibody associated encephalitis preceded by COVID-19 infection; a case study and systematic review of the literature | AntiNMDA | Scoop.it
From www.frontiersin.org - September 5, 2023 11:22 AM
BackgroundNew neurological complications of COVID-19 infection have been reported in recent research. Among them, the spectrum of anti-MOG positive diseases, defined as anti-MOG antibody associated disease (MOGAD), is distinguished, which can manifest as optic neuritis, myelitis, or various forms...
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Enceph-IG Study - Institute of Infection, Veterinary and Ecological Sciences - University of Liverpool

Enceph-IG Study - Institute of Infection, Veterinary and Ecological Sciences - University of Liverpool | AntiNMDA | Scoop.it
From www.liverpool.ac.uk - August 6, 2023 7:27 PM
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A Rare Presentation of Steroid-responsive Encephalopathy Associated with Autoimmune Thyroiditis with Neuropsychiatric Symptoms: A Case Report

A Rare Presentation of Steroid-responsive Encephalopathy Associated with Autoimmune Thyroiditis with Neuropsychiatric Symptoms: A Case Report | AntiNMDA | Scoop.it
From touchneurology.com - July 27, 2023 11:22 AM
A 42-year-old woman presented in the emergency department with acute onset whole-body myoclonic jerks for 1 day.On enquiry, the patient’s parents advised...
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Pioneering Research in Autoimmune Neurology: Vanda Lennon, M.D., Ph.D.

Pioneering Research in Autoimmune Neurology: Vanda Lennon, M.D., Ph.D. | AntiNMDA | Scoop.it
From news.mayocliniclabs.com - July 27, 2023 11:05 AM
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New center to spotlight neurological autoimmune disorders

New center to spotlight neurological autoimmune disorders | AntiNMDA | Scoop.it
From bioengineer.org - July 14, 2023 2:19 PM
How do neurological disorders arise that are caused, triggered, or influenced by antibodies? What better possibilities are there for diagnosis – and above all for treatment? These are the questions addressed by the new Clinical Research Unit “BecauseY” headed by Charité – Universitätsmedizin Berlin.
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Progressive alliance advances science through patient-powered research

Progressive alliance advances science through patient-powered research | AntiNMDA | Scoop.it
From news.mayocliniclabs.com - July 14, 2023 2:16 PM
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ENCEPH-IG Trial: The Challenges Of Running A Rare Disease Trial - Centre for Trials Research

ENCEPH-IG Trial: The Challenges Of Running A Rare Disease Trial - Centre for Trials Research | AntiNMDA | Scoop.it
From blogs.cardiff.ac.uk - June 19, 2023 9:46 PM
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30 neurological disorders every doctor should know about –

30 neurological disorders every doctor should know about – | AntiNMDA | Scoop.it
From theneurologylounge.com - June 19, 2023 9:42 PM
Neurology is a jungle of disorders and syndromes. This creates a challenge for doctors and medical students... What to prioritise for learning and practice? *** To solve this conundrum... We combed the extensive database of Neurochecklists...
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A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis

A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis | AntiNMDA | Scoop.it
From pubmed.ncbi.nlm.nih.gov - June 19, 2023 9:34 PM
The NEOS score accurately predicts 1-year functional status in patients with anti-NMDAR encephalitis. This score could help estimate the clinical course following diagnosis and may aid in identifying patients who could benefit from novel therapies.
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Canadian Blood Services needs thousands more donors to roll up their sleeves | CBC News

Canadian Blood Services needs thousands more donors to roll up their sleeves | CBC News | AntiNMDA | Scoop.it
From www.cbc.ca - June 19, 2023 9:28 PM
Canadian Blood Services is looking to fill 150,000 appointments for people willing to donate their blood or plasma to tackle a shortage.
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A catatonic woman awakened after 20 years. Her story may change psychiatry – My Health CRM

A catatonic woman awakened after 20 years. Her story may change psychiatry – My Health CRM | AntiNMDA | Scoop.it
From myhealthcrm.com - June 14, 2023 7:43 PM
New research suggests that a subset of patients with psychiatric conditions such as schizophrenia may actually have autoimmune disease that attacks the brain...
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Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases

Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases | AntiNMDA | Scoop.it
From pubmed.ncbi.nlm.nih.gov - June 14, 2023 7:41 PM
Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders...
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Medical Moment: The signs of ‘brain-on-fire’ disease

Medical Moment: The signs of ‘brain-on-fire’ disease | AntiNMDA | Scoop.it
From www.wndu.com - June 14, 2023 7:40 PM
(WNDU) - Imagine being totally fine one day, then the next, you’re having hallucinations, seizures, memory loss, and even trouble talking.It’s called “brain-on-fire” disease or anti-NMDA receptor encephalitis. It’s a rare neurological disorder that can cause inflammation in the brain.It occurs when the body’s immune system mistakenly attacks the NMDA receptors in the brain, which are responsible for regulating communication between nerve cells. Brain-on-fire disease is often misdiagnosed as other neurological disorders or psychiatric illnesses because its symptoms are similar to those of many other conditions.However, a blood or cerebrospinal fluid test can help diagnose the disease by detecting the presence of antibodies that attack the NMDA receptors in the brain. The disease is rare as it affects one in 1.5 million people a year.Katie Miller would be one of those people.Hunting, mountain biking, horseback riding - you name it, Katie Miler would do it... until she couldn’t.“I just didn’t feel like myself, like normal,” Katie recalled.“Katie said, ‘Mom, I feel like my brain snapped,’” said Colleen Miller, Katie’s mother.Local doctors admitted Katie into a psychiatric ward, but what was happening to Katie wasn’t mental; it was physical.“What happens is you’re perfectly normal one day, and suddenly overnight, this person can become paranoid, can start having visual hallucinations, auditory hallucinations,” explained Stacy Clardy, MD, PhD, an autoimmune neurologist at the University of Utah.Anti-NMDA receptor encephalitis is misdiagnosed as a psychiatric disorder in up to 40% of patients.“So, for many of the females, especially after puberty, they can develop what’s called an ovarian dermoid cyst or an ovarian teratoma,” Dr. Clardy said.These cysts often have hair and teeth in them. The immune system sees it as foreign and attacks it, but...“In these cysts, there is a component of tissue that really is brain tissue,” Dr. Clardy continued.Within four days, Katie was catatonic and needed a ventilator to breathe. There is no single approved treatment. That’s why a five-year, nationwide clinical trial is testing whether a drug called Inebilizumab will stop the assault on the brain. It has the potential to improve outcomes for patients who are not responding to other treatments and may also lead to fewer long-term neurological effects.Katie had her cyst removed; she can’t remember three months of her life. But now, with various medications, Katie is on her way to recovery.Up to 50% of patients can suffer long-term consequences, especially cognitive and mood symptoms.Copyright 2023 WNDU. All rights reserved.
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