Anti-NMDA receptor encephalitis in Japan: Long-term outcome without tumor removal

Department of Neurology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa, 228-8555, Japan.
Neurology (Impact Factor: 8.29). 03/2008; 70(7):504-11. DOI: 10.1212/01.wnl.0000278388.90370.c3
Source: PubMed


To report the definitive diagnosis of anti-NMDA receptor (NMDAR) encephalitis in four Japanese women previously diagnosed with "juvenile acute nonherpetic encephalitis" of unclear etiology, and to describe their long-term follow-up in the absence of tumor resection.
We extensively reviewed the case histories with current clinical and laboratory evaluations that include testing for antibodies to NR1/NR2 heteromers of the NMDAR in serum/CSF available from the time of symptom onset (4 to 7 years ago) and the present.
All patients sequentially developed prodromal symptoms, psychosis, hypoventilation, severe orofacial dyskinesias, and bizarre immunotherapy-resistant involuntary movements that lasted 1 to 12 months. Two patients required mechanical ventilation for 6 and 9 months. Initial tests were normal or unrevealing, including the presence of nonspecific CSF pleocytosis, and normal or mild changes in brain MRI. Eventually, all patients had dramatic recovery of cognitive functions, although one had bilateral leg amputation due to systemic complications. Antibodies to NR1/NR2 heteromers were found in archived serum or CSF but not in long-term follow-up samples. An ovarian teratoma was subsequently demonstrated in three patients (all confirmed pathologically).
1) These findings indicate that "juvenile acute nonherpetic encephalitis" or a subset of this disorder is mediated by an antibody-associated immune response against NR1/NR2 heteromers of the NMDA receptor (NMDAR). 2) Our patients' clinical features emphasize that anti-NMDAR encephalitis is severe but potentially reversible and may precede by years the detection of an ovarian teratoma. 3) Although recovery may occur without tumor removal, the severity and extended duration of symptoms support tumor removal.

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Available from: Takahiro Iizuka, May 26, 2015
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    • "However, further studies show that this occurs in both men and women, and many patients are nonparaneoplastic (Irani et al. 2010b). Clinically, a prodromal stage with symptoms, such as fever, nausea, vomiting, or diarrhea, can occur (Iizuka et al. 2008). Patients may then go onto developing seizures ( partial), status epilepticus, short-term memory loss, and, in addition, often show major psychiatric symptoms, such as anxiety, fear, mania, and paranoia. "
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    • "Although NR3 subunit can complex with NR1 subunit to form a glycine-responsive excitatory receptor, it does not bind glutamate (Chatterton et al. 2002). Initially, anti-NMDAR encephalitis, which is potentially lethal, manifests clinically as a range of psychiatric symptoms, and subsequently as intractable seizure disorders, dyskinesia, autonomic instability or hypoventilation (Dalmau et al. 2007, 2008; Iizuka et al. 2008). An anti-neural antibody for the NR1/NR2 heteromer of NMDARs has been identified as a disease-specific hallmark (Vitaliani et al. 2005; Dalmau et al. 2008). "
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    • "De manière moins spécifique, le LCR révèle une pléïocytose lymphocytaire, une hyperprotéinorachie, associées à des bandes oligoclonales [4] [5] [6] [7]. Les examens complémentaires doivent systématiquement rechercher une étiologie tumorale à l'encéphalite [1] [3] [4]. Il est donc recommandé de réaliser, à visée systématique, une IRM pelvienne, un TEP-Scan corps entier, une imagerie thoracoabdomino-pelvienne , une échographie pelvienne plus ou moins endo-vaginale chez la fille, une échographie testiculaire chez le garçon. "
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