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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Leukocyte mitochondrial DNA A to G polymorphism at 11084 is not a risk factor for Japanese migraineurs.

Mitochondrial dysfunction has been reported in patients with migraine. We investigated leukocyte mitochondrial DNA 11084 A to G polymorphism in 166 Japanese migraineurs and 483 Japanese controls. The migraine group consisted of 43 patients suffering from migraine with aura (MWA) and 123 from migraine without aura (MOA). The frequency of the transition was 7.2% (12/166) in the migraine group and 7.3% (35/483) in the controls. The frequency of the transition was 4.7% in MWA and 8.1% in MOA. There was no significant difference among the groups (chi-square test). The mitochondrial DNA 11084 A to G transition was more common in Japanese subjects than reported in Caucasians; however, this polymorphism is not a genetic risk factor for migraine in Japanese patients.