Announcement

**Emily** · April 8, 2010, 02:16 AM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

http://www.primarypsychiatry.com/asp...articleid=1677

Psychosis Associated with Anti-N-methyl-D-aspartate Receptor Antibodies
Kevin M. Nasky, DO, Douglas R. Knittel, MD, and Gail H. Manos, MD
CNS Spectr. 2008;13(8):699-702
Until recently, relatively few reports have associated the etiology of limbic encephalitis with the production of antibodies to the N-methyl-D-aspartate (NR)1/NR2 subunit heterodimers of the N-methyl-D-aspartate (NMDA) receptor. In fact, 13 out of the 23 total publications on the subject of anti-NMDA receptor encephalitis appeared in 2007, revealing a sharp increase in the incidence of this disorder, its recognition, or both.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607118/

Lancet Neurol. 2008 December; 7(12): 1091–1098.
Published online 2008 October 11. doi: 10.1016/S1474-4422(08)70224-2.

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

In anti-NMDA-receptor encephalitis the high prevalence of prodromal viral-like symptoms is intriguing. Direct viral pathogenesis is unlikely because extensive studies of CSF samples, brain biopsies, and autopsies were negative for viruses (data not shown). Whether the prodromal symptoms form part of an early immune activation,17,18 or result from a non-specific infection that facilitates crossing of the blood–brain barrier by the immune response is unknown.19,20 Nevertheless, the immune response eventually predominates in the nervous system as suggested by the high frequency of pleocytosis, oligoclonal bands, and intrathecal synthesis of NR1 antibodies. In general, patients with an underlying tumour develop more robust immune responses than those without a tumour.
...
A characteristic feature of patients who recover from anti-NMDA-receptor encephalitis is a persisting amnesia of the entire process (data not shown). This feature is compatible with disruption of the mechanisms of synaptic plasticity, thought to underlie learning and memory, in which the NMDA receptors play a key part.
....
Anti-NMDA-receptor encephalitis represents a new category of immune-mediated disorder that is often paraneoplastic, treatable, and can be diagnosed serologically. Future studies should clarify the best type and duration of immunotherapy, the role of prodromal events in triggering the immune response, and the molecular mechanisms involved in decreasing the number of NMDA receptors.

http://www.ncbi.nlm.nih.gov/pubmed/2...gdbfrom=pubmed

Nervenarzt. 2010 Jan 31. [Epub ahead of print]
[Anti-NMDA-receptor encephalitis : An interdisciplinary clinical picture.]

[Article in German]

Prüß H, Dalmau J, Arolt V, Wandinger KP.

Experimentelle Neurologie und Klinik und Poliklinik für Neurologie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.

Anti-NMDA-receptor encephalitis is a severe and considerably underdiagnosed form of encephalitis with characteristic clinical features including psychiatric symptoms, decreased levels of consciousness, hypoventilation, epileptic seizures, autonomic dysfunction and dyskinesias. Most patients are primarily seen by psychiatrists, often on the assumption of a drug-induced psychosis. Anti-NMDA-receptor encephalitis had initially been described in young women with ovarian teratoma, but is also common in women without tumour, in men and in children.

I see quite a few parents of very young children looking for support and information about this.
http://www.facebook.com/group.php?v=...d=116113262677

**sharon sanders** · April 8, 2010, 09:28 AM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

Thanks Emily.

**Emily** · April 20, 2010, 12:22 AM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

http://journals.lww.com/co-neurology...ion_of.10.aspx

Current Opinion in Neurology:
April 2010 - Volume 23 - Issue 2 - p 144–150
doi: 10.1097/WCO.0b013e32833735fe
Seizure disorders: Edited by Michael Sperling
The growing recognition of immunotherapy-responsive seizure disorders with autoantibodies to specific neuronal proteins
Vincent, Angela; Irani, Sarosh R; Lang, Bethan

**Emily** · April 23, 2010, 06:47 PM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

http://www.ncbi.nlm.nih.gov/pubmed/20016378

Crit Care Med. 2010 Feb;38(2):679-82.
Anti-N-methyl-D-aspartate receptor antibodies: a potentially treatable cause of encephalitis in the intensive care unit.

Davies G, Irani SR, Coltart C, Ingle G, Amin Y, Taylor C, Radcliffe J, Hirsch NP, Howard RS, Vincent A, Kullmann DM.

National Hospital for Neurology and Neurosurgery, and Institute of Neurology, University College London, London, UK.
Abstract

OBJECTIVE: To report the occurrence of an unusual neurologic disorder requiring admission to the intensive care unit. DESIGN: Analysis of an observational cohort study of 31 patients with encephalitis admitted over a 4-yr period. SETTING: Neurologic intensive care unit in a tertiary referral center. PATIENTS: We identified N-methyl-D-aspartate receptor antibodies in six patients (two male and four female). All seropositive patients presented with a psychiatric prodrome, before developing seizures and obtundation requiring intensive care unit admission. They exhibited limb and truncal stereotypies and orofacial dyskinesias upon weaning sedation. Two patients had ovarian tumors. INTERVENTIONS: Patients were treated with sedation, antiepileptic drugs, and immunotherapy. One patient received a magnesium infusion and ketamine. MEASUREMENTS AND MAIN RESULTS: N-methyl-D-aspartate receptor antibodies were identified in serum samples by an immunofluorescent cell-based assay. Three patients made a good but slow recovery; two were left with severe neurologic deficits; and one died after return to the referring hospital. These patients accounted for approximately 20% of all patients admitted with encephalitis to this referral center. CONCLUSIONS: N-methyl-D-aspartate receptor antibodies should be tested in patients with hyperkinetic encephalitis and neuropsychiatric prodrome admitted to the intensive care unit. The disorder is probably not rare and is potentially treatable.

PMID: 20016378 [PubMed - indexed for MEDLINE]

http://www.news-bulletin.com/nb/inde...y-illness.html

Mother seeks help with child's mystery illness
Written by Brent Ruffner/News-Bulletin
Wednesday, 07 April 2010 06:00

Desiree Egan-Jaramillo gently held her daughter's hand after putting her into a red Flyer wagon on a recent Thursday afternoon.

But her daughter, Fiona, wasn't on her way to an Easter egg hunt or an afternoon of playing in the park with her friends.

Instead, the 3-year old was asleep on the sixth floor of the University of New Mexico Children's Hospital, likely catching her breath from a day full of medical testing.

The pair have been at the hospital since Jan. 22, the day Fiona suddenly stopped breathing and was rushed to the Albuquerque hospital after sporadic spells of flu-like symptoms in the weeks before.....continued at link

**Emily** · April 24, 2010, 01:50 AM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

http://www.ncbi.nlm.nih.gov/pubmed/19718525

Eur J Clin Microbiol Infect Dis. 2009 Dec;28(12):1421-9. Epub 2009 Aug 29.
Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis.

Gable MS, Gavali S, Radner A, Tilley DH, Lee B, Dyner L, Collins A, Dengel A, Dalmau J, Glaser CA.

Department of Psychiatry, University of California San Francisco, Fresno, CA, USA.
Abstract

The California Encephalitis Project (CEP), established in 1998 to explore encephalitic etiologies, has identified patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, the likely etiology of their encephalitis. This study compares the presentation of such patients to those with viral encephalitis, so that infectious disease clinicians may identify individuals with this treatable disorder. Patients were physician-referred, and standardized forms were used to gather demographic, clinical, and laboratory data. Features of anti-NMDAR+ patients were compared with the viral encephalitides of enteroviral (EV), rabies, and herpes simplex-1 (HSV-1) origins. Sixteen cases with confirmed viral etiologies were all negative on NMDAR antibody testing. Ten anti-NMDAR+ patients were profiled with a median age of 18.5 years (range 11-31 years). None were Caucasian. They had a characteristic progression with prominent psychiatric symptoms, autonomic instability, significant neurologic abnormalities, and seizures. Two had a teratoma, and, of the remaining eight, four had serologic evidence of acute Mycoplasma infection. The clinical and imaging features of anti-NMDAR+ patients served to differentiate this autoimmune disorder from HSV-1, EV, and rabies. Unlike classic paraneoplastic encephalitis, anti-NMDAR encephalitis affects younger patients and is often treatable. The association of NMDAR antibodies in patients with possible Mycoplasma pneumoniae infection warrants further study.

PMID: 19718525 [PubMed - indexed for MEDLINE]PMCID: PMC2773839

http://www.medlink.com/medlinkcontent.asp

Neurologic complications of Mycoplasma pneumoniae infection

By John E Greenlee
Last reviewed
December 7, 2009

....
Postinfectious complications of Mycoplasma pneumoniae infection. In addition to presentation with meningitis or encephalitis, a large number of patients have been reported with neurologic events occurring in association with M pneumoniae infection. These include psychosis, acute disseminated encephalomyelitis, brainstem encephalitis, cerebellar ataxia, diffuse or transverse myelitis, a poliomyelitis-like syndrome, optic neuritis, radiculopathies, and brachial plexopathies
.....

**Emily** · May 15, 2010, 06:28 PM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

Post here on a support forum from April 28, 2010 about a toddler with the illness.

http://www.inspire.com/groups/enceph...ncephalitis-1/

**Emily** · May 28, 2010, 02:25 AM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

http://www.ncbi.nlm.nih.gov/pubmed/20420172

Brain Nerve. 2010 Apr;62(4):331-8.
[Update on anti-NMDA receptor encephalitis]

[Article in Japanese]

Iizuka T, Sakai F, Mochizuki H.

Department of Neurology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Abstract

A new category of treatment-responsive encephalitis has been proposed in association with antibodies to neuronal cell membrane antigens, including voltage-gated potassium channel (VGKC), N-methyl-D-aspartic acid receptor (NMDAR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid (GABA) B receptor and other antigens that have not yet been characterized. Among the forms of encephalitis under this category, anti-NMDAR encephalitis is a distinct disorder characterized by the predictable sequential development of symptoms; prodromal symptoms are initially noted, followed by prominent psychiatric symptoms, seizures, an unresponsive/catatonic state, hypoventilation, and involuntary orofacial-limb movements. This disorder usually affects young women with ovarian teratoma but may also affect women of any age or even men. A recent study revealed that the main epitope targeted by anti-NMDAR antibodies lies in the extracellular N-terminal domain of the NR1 subunit (25-380 amino-acid residues); the NR2B subunit is not necessarily involved. The antibodies are shown to produce selectively and reversibly reduce postsynaptic NMDARs clusters without complement activation. Considering the symptomatology of anti-NMDAR encephalitis and the results of cell culture analysis, we speculate that the overall antibody-mediated inhibition of NMDARs expressed on GABAergic interneurons, glutamatergic neurons and dopaminergic neurons may cause neuropsychiatric symptoms and dyskinesias via dopamine and glutamate dysregulation. We also hypothesize that these antibodies affect not only trafficking/localization/clustering of postsynaptic NMDARs, but also the expression of other receptors including AMPAR and dopamine receptors, by including a chronic state of exposure to excessive or decreased neurotransmitters release. The establishment of an animal model is awaited to resolve these issues. Anecdotal reports have revealed that recovery may be spontaneous without tumor resection but early tumor resection along with aggressive immunotherapy facilitates early functional recovery. In a recent case, a microscopic teratoma was detected on autopsy; therefore exploratory laparotomy may be considered in severe refractory cases.

**Emily** · May 29, 2010, 12:28 AM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

Full text and supplementary material at link.

http://www.ncbi.nlm.nih.gov/pmc/arti...5/?tool=pubmed

Ann Neurol. Author manuscript; available in PMC 2010 February 22.
Published in final edited form as:
Ann Neurol. 2009 July; 66(1): 11?18.
doi: 10.1002/ana.21756.

PMCID: PMC2826225
NIHMSID: NIHMS173684

Anti?N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis in Children and Adolescents
Nicole R. Florance, MD,1 Rebecca L. Davis, BA,2 Christopher Lam, MD,3 Christina Szperka, MD,1 Lei Zhou, BS,2 Saba Ahmad, MD,1 Cynthia J. Campen, MD,1 Heather Moss, MD, PhD,2 Nadja Peter, MD,4 Amy J. Gleichman, BS,5 Carol A. Glaser, MD,6 David R. Lynch, MD, PhD,1,2 Myrna R. Rosenfeld, MD, PhD,2 and Josep Dalmau, MD, PhD2
1Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA
2Department of Neurology, University of Pennsylvania, Philadelphia, PA
3Division of Psychiatry, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA
4Division of Adolescent Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA
5Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA
6Viral and Rickettsial Disease Laboratory, Division of Communicable Disease Control, Center of Infectious Disease, California Department of Public Health, Richmond, CA
Objective
To report the clinical features of anti?N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients ≤ 18 years old.
Methods
Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1.
Results
Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were ≤18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls ≤18 years old (p = 0.05), and 9% in girls ≤14 years old ( p = 0.008). None of the male patients had tumors. Of 32 patients ≤18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03).
Interpretation
Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children.

There's a short video on this topic here.
http://www.medscape.com/viewarticle/718090
Anti-N-methyl-D-aspartate Receptor Encephalitis
Kapil D. Sethi, MD
Posted: 03/15/2010

**Emily** · June 16, 2010, 03:04 PM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

First case diagnosed in India is reported here:

http://www.flutrackers.com/forum/sho...d.php?t=147956

**Emily** · June 20, 2010, 03:21 PM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

There is no abstract available on this.
http://www.neurology.org/cgi/content.../18/1473?rss=1

Neurology, Vol. 74, Issue 18, 1473-1475, May 4, 2010

CLINICAL/SCIENTIFIC NOTES
NMDA RECEPTOR ENCEPHALITIS MIMICKING SERONEGATIVE NEUROMYELITIS OPTICA

M.C. Kruer, T.K. Koch, D.N. Bourdette, D. Chabas, E. Waubant, S. Mueller, M.A. Moscarello, J. Dalmau, R.L. Woltjer, and G. Adamus

This is a study done in the UK.

http://www.ncbi.nlm.nih.gov/pubmed/20511282

Brain. 2010 Jun;133(Pt 6):1655-67.
N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes.

Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS, Friese MA, Galea I, Kullmann DM, Beeson D, Lang B, Bien CG, Vincent A.

Department of Clinical Neurology, L6 West Wing, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Abstract

Antibodies to the N-methyl-d-aspartate subtype of glutamate receptor have been associated with a newly-described encephalopathy that has been mainly identified in young females with ovarian tumours. However, the full clinical spectrum and treatment responses are not yet clear. We established a sensitive cell-based assay for detection of N-methyl-d-aspartate receptor antibodies in serum or cerebrospinal fluid, and a quantitative fluorescent immunoprecipitation assay for serial studies. Although there was marked intrathecal synthesis of N-methyl-d-aspartate receptor antibodies, the absolute levels of N-methyl-d-aspartate receptor antibodies were higher in serum than in cerebrospinal fluid. N-methyl-d-aspartate receptor antibodies were of the immunoglobulin G1 subclass and were able to activate complement on N-methyl d-aspartate receptor-expressing human embryonic kidney cells. From questionnaires returned on 44 N-methyl-d-aspartate receptor antibody-positive patients, we identified a high proportion without a detected tumour (35/44, 80%: follow-up 3.6-121 months, median 16 months). Among the latter were 15 adult females (43%), 10 adult males (29%) and 10 children (29%), with four in the first decade of life. Overall, there was a high proportion (29%) of non-Caucasians. Good clinical outcomes, as defined by reductions in modified Rankin scores, correlated with decreased N-methyl-d-aspartate receptor antibody levels and were associated with early (<40 days) administration of immunotherapies in non-paraneoplastic patients (P < 0.0001) and earlier tumour removal in paraneoplastic patients (P = 0.02). Ten patients (23%) who were first diagnosed during relapses had no evidence of tumours but had received minimal or no immunotherapy during earlier episodes. Temporal analysis of the onset of the neurological features suggested progression through two main stages. The time of onset of the early features, characterized by neuropsychiatric symptoms and seizures preceded by a median of 10-20 days, the onset of movement disorders, reduction in consciousness and dysautonomia. This temporal dichotomy was also seen in the timing of cerebrospinal fluid, electroencephalographic and in the rather infrequent cerebral imaging changes. Overall, our data support a model in which the early features are associated with cerebrospinal fluid lymphocytosis, and the later features with appearance of oligoclonal bands. The immunological events and neuronal mechanisms underlying these observations need to be explored further, but one possibility is that the early stage represents diffusion of serum antibodies into the cortical grey matter, whereas the later stage results from secondary expansion of the immunological repertoire within the intrathecal compartment acting on subcortical neurons. Four patients, who only had temporal lobe epilepsy without oligoclonal bands, may represent restriction to the first stage.

**Emily** · June 20, 2010, 06:03 PM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

http://www.ncbi.nlm.nih.gov/pubmed/20196492

Rinsho Shinkeigaku. 2010 Feb;50(2):103-7.
[Anti-NMDA receptor encephalitis during pregnancy]

[Article in Japanese]

Ito Y, Abe T, Tomioka R, Komori T, Araki N.

Department of Neurology, Faculty of Medicine, Saitama Medical University.
Abstract

A 19-year-old female in her 2nd trimester (17 weeks) of pregnancy became irritable a few days before admission. She became unable to open her mouth and could not talk. She was admitted to the psychiatric hospital due to a rapid change in behavior and a consciousness disturbance. She was diagnosed as having schizophrenia by a psychiatrist. Her EEG showed diffuse high voltage and slow waves. Acute encephalitis was then suspected. Her past and family histories were not suggestive of viral infection. On physical examination, she had a low grade fever. She had hyperhidrosis, autophagia, and repeated oral dyskinesia. Her consciousness level fluctuated from somnolence to stupor. Although her blood CRP level was mildly elevated and she had mild pleocytosis, HSV-PCR was negative in the cerebrospinal fluid (CSF). Abdominal ultrasound examination and MRI showed no ovarian teratoma. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no brain abnormalities. Before analysis for specific nervous system antibodies, the initial diagnosis was non-herpetic limbic encephalitis. She was twice treated with a 6-day course of methylprednisolone (500 mg/day) infusion. She was also given phenobarbital since she had a tonic-clonic seizure about 1 month after admission. Finally, she had a normal delivery at 37 weeks. The baby was healthy, and the patient was discharged without sequelae. We concluded that her diagnosis was anti-N-methyl-D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis based on the presence of anti-NMDAR antibody in the CSF. This report is the first description of a patient with anti-NMDAR antibody encephalitis. The precise mechanism of this encephalitis is not clear, although there have been several reports of autoimmune encephalitis during pregnancy. The patient's CSF anti-NMDAR antibody titer during treatment was measured. Before treatment, the CSF anti-NMDAR antibody titer was strongly positive, but it decreased during treatment and then disappeared after delivery. We hypothesized that the presence of the embryo or placenta may have triggered an antigenic signal and/or antibody through inappropriate immunological modulation.

**Emily** · June 20, 2010, 07:46 PM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

What we're learning about NMDAR encephalitis might solve a mystery surrounding the 1918 influenza pandemic era.

http://www.ncbi.nlm.nih.gov/pubmed/19938173

Ann Neurol. 2009 Nov;66(5):704-9.
N-methyl-D-aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica.

Dale RC, Irani SR, Brilot F, Pillai S, Webster R, Gill D, Lang B, Vincent A.

Neuroinflammation Group, Institute for Neuroscience and Muscle Research, the Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Westmead, Australia.
Abstract

Encephalitis lethargica (EL) describes an encephalitis with psychiatric, sleep, and extrapyramidal movement disorders. Dyskinetic and parkinsonian forms have been described. EL shares clinical features with the anti-N-methyl-D-aspartate receptor (NMDAR-Ab) encephalitis. We studied 20 sera from pediatric patients with contemporary EL. Ten sera (from 2 males and 8 females, aged 1.3-13 years) and 6/6 cerebrospinal fluid samples were positive for NMDAR-Ab. NMDAR-Ab-positive patients had dyskinesias, agitation, seizures, and insomnia, whereas parkinsonism and somnolence dominated in the NMDAR-Ab-negative children. We were unable to identify any tumors. The dyskinetic form of EL is an NMDAR-Ab encephalitis and can affect very young children.

Back in 2003 they were already investigating EL as being from immune dysfunction rather than viral origin:

http://www.ncbi.nlm.nih.gov/pubmed/14570817

Brain. 2004 Jan;127(Pt 1):21-33. Epub 2003 Oct 21.
Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity.

Dale RC, Church AJ, Surtees RA, Lees AJ, Adcock JE, Harding B, Neville BG, Giovannoni G.

Neurosciences Unit, Great Ormond Street Hospital and Institute of Child Health, and Department of Neuroinflammation, Institute of Neurology, University College London, UK.

Comment in:

* Brain. 2004 Jan;127(Pt 1):2-3.

Abstract

In 1916, von Economo first described encephalitis lethargica (EL), a CNS disorder presenting with pharyngitis followed by sleep disorder, basal ganglia signs (particularly parkinsonism) and neuropsychiatric sequelae. Since the 1916-1927 epidemic, only sporadic cases have been described. Pathological studies revealed an encephalitis of the midbrain and basal ganglia, with lymphocyte (predominantly plasma cell) infiltration. The EL epidemic occurred during the same time period as the 1918 influenza pandemic, and the two outbreaks have been linked in the medical literature. However, von Economo and other contemporary scientists thought that the 1918 influenza virus was not the cause of EL. Recent examination of archived EL brain material has failed to demonstrate influenza RNA, adding to the evidence that EL was not an invasive influenza encephalitis. By contrast, the findings of intrathecal oligoclonal bands (OCB) and beneficial effects of steroid treatments have provoked the hypothesis that EL may be immune-mediated. We have recently seen 20 patients with a similar EL phenotype, 55% of whom had a preceding pharyngitis. The patients had remarkable similarity to the historical descriptions of EL: sleep disorder (somnolence, sleep inversion or insomnia), lethargy, parkinsonism, dyskinesias and neuropsychiatric symptoms. CSF examination commonly showed elevated protein and OCB (75 and 69% respectively). Investigation found no evidence of viral encephalitis or other recognized causes of rapid-onset parkinsonism. MRI of the brain was normal in 60% but showed inflammatory changes localized to the deep grey matter in 40% of patients. We investigated the possibility that this phenotype could be a postinfectious autoimmune CNS disorder, and therefore similar to Sydenham's chorea. Anti-streptolysin-O titres were elevated in 65% of patients. Furthermore, western immunoblotting showed that 95% of EL patients had autoantibodies reactive against human basal ganglia antigens. These antibodies were also present in the CSF in four patients tested. By contrast, antibodies reactive against the basal ganglia were found in only 2-4% of child and adult controls (n = 173, P < 0.0001). Rather than showing polyspecific binding, these antibodies bound to common neural autoantigens of molecular weight 40, 45, 60 and 98 kDa. Regional tissue comparisons showed that the majority of these autoantigens were specific to or enriched in CNS tissue. Immunohistochemistry with secondary staining localized antibody binding to neurons rather than glial populations. Further investigation is required to determine whether these antibodies affect neuronal function (i.e. whether they are pathogenic anti-neuronal antibodies). Histopathology in one case demonstrated striatal encephalitis with perivenous B- and T-lymphocytic infiltration. We believe an EL-like syndrome is still prevalent, and propose that this syndrome may be secondary to autoimmunity against deep grey matter neurons.

**Anne** · June 21, 2010, 01:01 AM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

Thank you Emily.
I was interested by Lethargica which was a horrible epidemic.

I do not know if this has something to do, but it has been proved recently that narcolepsy is an autoimmune disease.

**Emily** · July 18, 2010, 05:41 PM

Re: Anti-NMDA receptor encephalitis: an emerging autoimmune brain disease

I didn't know that about narcolepsy, Anne. That's very interesting that it is another mysterious brain illness that is triggered by autoimmunity. I searched around after reading your post, and there is some hope that early immune treatment might be effective in that disease, too.

I was thinking about the EL outbreak from 1916-1927 and if it was not caused by the flu strain then, I wondered about wartime toxins. Also we discussed here that the medicines used to treat the flu at the time were arsenic based. In a panic over the flu epidemic I'd guess medicines could be overused.

I wish we knew more about what caused that outbreak of EL, so we might have more insight into what is causing the anti-NMDAR encephalitis. When you search for that term, this comes up.
http://ccforum.com/content/14/3/222/abstract
Ethics roundtable: 'Open-ended ICU care: Can we afford it?'

I can't access the article, but what I'm assuming they are discussing is sad given that the patients are very young.

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Anti-NMDA receptor encephalitis and other emerging autoimmune brain diseases

Anti-NMDA receptor encephalitis and other emerging autoimmune brain diseases

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