Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis

Abstract

We report an 18-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms, progressive unresponsiveness, dyskinesias, hypoventilation, hypersalivation and seizures. Early removal of an ovarian teratoma followed by plasma exchange and corticosteroids resulted in a prompt neurological response and eventual full recovery. Serial analysis of antibodies to NR1/NR2B heteromers of the NMDAR showed an early decrease of serum titres, although the cerebrospinal fluid titres correlated better with clinical outcome. The patients' antibodies reacted with areas of the tumour that contained NMDAR-expressing tissue. Search for and removal of a teratoma should be promptly considered after the diagnosis of anti-NMDAR encephalitis.Paraneoplastic encephalitis associated with ovarian teratoma has recently been related to the development of antibodies to the NR1/NR2B heteromers of the N-methyl-D-asparate receptor (NMDAR). 1 The disorder, called anti-NMDAR encephalitis, results in a characteristic syndrome that presents with prominent psychiatric symptoms or, less frequently, memory deficits, followed by a rapid decline of the level of consciousness, central hypoventilation, seizures, involuntary movements and dysautonomia. Despite the severity of symptoms and prolonged clinical course, most patients recover if the disorder is recognised and treated. 1 Immunotherapy, including corticosteroids, intravenous immunoglobulin or plasma exchange, is often effective, and it has been suggested that prompt resection of the teratoma expedites recovery. 1 In most previously reported cases of anti-NMDAR encephalitis, the ovarian teratoma was removed a few months (median: 9 weeks) after neurological symptom presentation, sometimes when symptoms had already partially responded to immunotherapy. 1-5 We report the clinical outcome and follow-up of antibody titres in a Japanese woman whose ovarian tumour was removed early (20 days) after neurological symptom onset. CASE REPORTAn 18-year-old woman without a past medical history of interest developed headache and fever for a few days. She also complained of the sensation that the left half of her body was twisting. She was admitted to our hospital with progressive psychosis, and emotional and behavioural changes. Her temperature was 37.1°C; no meningeal signs were noted. Sustained involuntary movements were observed around her mouth, resembling orofacial dyskinesias. She was disorientated to place and person, and had schizophrenia-like symptoms, such as disorganized 1). She constantly repeated "I'm in the world of Harry Potter!" and "I have no idea who I am!" and knocked her head against the wall. Intravenous administration of acyclovir (1500 mg/day) and dexamethasone (6 mg/day) resulted in no improvement and she became mute and unresponsive to verbal commands. The orofacial dyskinesias gradually worsened, showing sustained bizarre movements such as widely opening and tightly closing of the eyes and mouth, sticking out the tongue and grimacin...

Nationwide Survey of Acute Juvenile Female Non-Herpetic Encephalitis in Japan: Relationship to Anti-N-Methyl-D-Aspartate Receptor Encephalitis

“…However, several problems still remain to be unresolved including the etiology of patients without anti-NMDAR antibody, the etiology of male patients, the lack of detectable ovarian teratomas in some patients, the reason why predominantly young adults are affected, the reason why many Japanese patients are reported (4,(8)(9)(10), and the reason why there is a good outcome in the long term without tumor removal.…”

Complete recovery from paraneoplastic anti-NMDAR encephalitis associated with a small ovarian teratoma following a laparoscopic salpingo-oophorectomy: A case report

“…Removal of the NMDAR-expressing tumor reduces the serum and cerebrospinal fluid levels of the pathological autoantibody (10). The present case report demonstrates that complete recovery from the severe neurological symptoms of anti-NMDAR encephalitis is possible following surgical resection.…”

Clinical Aspects of Anti-NMDA Receptor Encephalitis

“…Ovarian tumor removal in the acute phase Seki et al, 2008), chemotherapy for the tumors (Eker et al, 2008), cyclophosphamide Wilder-Smith and Ng, 2008), and rituximab (Ishiura et al, 2008) were also effective treatments for a small number of cases. In our cases (Table 1), corticosteroids were administered to four cases, and high-dose intravenous gammaglobulin to three cases.…”

“…They diagnosed and reported twelve women (including our case) as having 'paraneoplastic anti-NMDA receptor encephalitis associated with an ovarian teratoma', the cases developing prominent psychiatric symptoms, amnesia, seizures, frequent dyskinesias, autonomic dysfunction, and a decreased level of consciousness often requiring ventilatory support . After this publication, several reports about anti-NMDA receptor encephalitis have appeared in Japan Seki et al, 2008;Kataoka, Dalmau, and Ueno, 2008;Ishiura et al, 2008;Shindo et al, 2009). Analysis of a worldwide one hundred anti-NMDA receptor encephalitis case series revealed that about 60% of them had associated tumors such as ovarian teratomas .…”