Transplacental transfer of NMDA receptor antibodies in an infant with cortical dysplasia

Abstract

A confused and agitated 18-year-old woman presented to the emergency unit with orolingual movements, eye deviation, and a temperature of 38°C. The symptoms had begun 2 weeks prior to the admission when she developed a severe headache associated with pathologic laughing and intermittent episodes of upgaze deviation. A urine pregnancy test was positive and a transvaginal ultrasonography showed a 9-week-old fetus. An MRI of the brain was unremarkable and results of the CSF analysis were also unremarkable apart from a CSF pleocytosis (62 lymphocytes) and slightly elevated protein (55 mg/dL; normal range 0-45 mg/dL). Extensive microbiologic and serologic studies with CSF were all negative. She gradually lost consciousness, experienced respiratory failure, and was intubated. There were semirhythmic movements consisting of complex patterns of mouth opening, chewing, facial grimacing, synchronous flexion-extension, and supination-pronation limb movements, which persisted during the period of unresponsiveness. She also had generalized hyperreflexia, persistent hyperthermia, and a full bladder. Three EEGs showed diffuse slow waves with no epileptic discharges. A diagnosis of anti-NMDA receptor (NMDAR) encephalitis was made on clinical grounds and strongly positive serum NMDAR antibodies.

Maternal-Fetal Transfer of Anti–N-Methyl-D-Aspartate Receptor Antibodies

“…6,11 This process starts slowly at the end of the first trimester and early second trimester and progressively increases until term. 8 Our patient delivered with positive antibody titers during a period of fetal vulnerability, and we confirmed transfer of maternal antibodies to fetal circulation. However, there are no data available on short-term or long-term consequences of prenatal NMDA receptor antibody exposure.…”

“…It is becoming more commonly recognized as a cause of encephalitis in young adults. 2,5,6 Very few cases have been described in pregnancy, [6][7][8][9][10] and only one fetus has been extensively evaluated for antibodies, the results of which were negative. This syndrome generally presents in five phases.…”

“…This syndrome generally presents in five phases. 8 These antibody subtypes are capable of crossing the placenta, and there remains concern for fetal effects. This is followed by the psychotic phase, seizure phase (or both), an unresponsive phase, and a hyperkinetic phase, characterized by autonomic instability.…”

Seizures and Epilepsies due to Channelopathies and Neurotransmitter Receptor Dysfunction: A Parallel between Genetic and Immune Aspects

“…One report of a transplacental transfer of NMDAR antibodies in a child who was later diagnosed with abnormal neonatal movements, developmental delay, seizures, and cortical dysplasia has been published recently [Jagota et al, 2014]. The question whether all or part of this child's clinical symptoms and findings result from the transfer of maternal antibodies remains unanswered.…”

Antibodies as Mediators of Brain Pathology

“…It should be mentioned that additional maternal anti-NMDAR antibodies against GluN1 have been described as leading to cortical dysplasia in offspring in NMDA encephalitis [118]. …”