A Rare Case of Anti-N-Methyl-D-Aspartate Receptor Encephalitis in an Infant Presenting with Regression and Movement Disorder.

Abstract

Dear Editor, Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is a potentially reversible, immune-mediated cause of encephalitis that is particularly common in children and young adults and may be the second most common cause of autoimmune encephalitis in the pediatric population.[1] In a large study of 577 patients with anti-NMDA receptor encephalitis, the median age at presentation was 21 years and 37% were younger than 18 years.[2] Although this entity is common in children, its occurrence in infants has been reported only rarely.[3–5] We describe the details of an 11-month-old boy with anti-NMDA receptor encephalitis. An 11-month-old boy born of non-consanguineous parentage and with uneventful perinatal history presented with regression of milestones following a febrile episode. His development was appropriate for his age prior to the onset of illness. He had high-grade fever for which he was treated at another hospital and improved in a few days. However, no serum or cerebrospinal fluid (CSF) encephalitis workup was conducted. Two weeks later, he developed regression of milestones. He lost neck control and was unable to sit even with support. He could only make incomprehensible sounds and social smile was also lost. Two weeks into the illness, he developed irritability, restlessness, and excessive movements of both the upper and lower limbs. He also developed repetitive movements of both the upper limbs in the form of thrusting of hands into the mouth and involuntary movements of the neck in the form of backward bending. He did not have seizures, altered sensorium, or paucity of movements in the limbs. There was no vomiting. His visual tracking was preserved and he could turn head to sounds. He did not have any other medical illness and there was no history of neurological illness in the family. His vital parameters and systemic examination were normal. His anthropometric measurements were age-appropriate. He was alert but irritable, restless, and crying continuously. He was able to maintain eye contact and turned his head to sounds. He was moving all four limbs. He had dystonia of the neck and stereotypies of both upper limbs in the form of thrusting of hands into the mouth. He was unable to hold his neck or sit even with support. Tone and reflexes in the limbs were normal. Plantar response was extensor bilaterally. Clinically, the differential diagnoses considered were neurometabolic disorders, epileptic encephalopathy, and post-infectious immune-mediated diseases. Hemogram and biochemical parameters were normal. Magnetic resonance imaging (MRI) of the brain [Figure 1] with contrast was normal. Electroencephalography (EEG) showed generalized spike-wave discharges with occasional burst-attenuation pattern [Figure 2]. Neurometabolic investigations (serum ammonia, lactate, screening for inborn errors of metabolism by tandem mass spectroscopy, and urine for abnormal metabolites) were not contributory. CSF analysis showed normal protein, sugar, and cell count. Anti-NMDA receptor antibody levels (based on transfected cell culture method) in the serum and CSF were strongly positive. The patient did not undergo any other evaluation for viral encephalitis in the CSF in view of normal MRI, and generalized spike-wave discharges with occasional burst-attenuation pattern in EEG. Ultrasound abdomen and chest X-ray were normal. Based on the clinical syndrome of developmental regression and new onset movement disorder following a prodromal febrile illness and positive antibody in CSF and serum, a diagnosis of anti-NMDA receptor antibody-mediated encephalitis was made.Figure 1: MRI brain axial sections T1- and T2-weighted images showing normal signal intensity in bilateral hippocampi and mesial temporal structuresFigure 2: EEG shows generalized spike-wave discharges with occasional burst-attenuation patternThe child was treated with intravenous methylprednisolone at 30 mg/kg every day for five days followed by intravenous immunoglobulin at 2 gm/kg divided over five days. Subsequently, he showed significant improvement in the form of reduced restlessness and irritability, regaining of milestones (in the form of ability to hold the neck and sit and stand with support and develop a social smile). There was improvement in cervical dystonia and upper limb stereotypies. He was advised monthly pulsed intravenous methylprednisolone to maintain remission. At the last follow-up, at the age of two years, developmental milestones were normal and he did not have any involuntary movements. Our patient presented with developmental regression and movement disorder following a febrile illness. The differentials of an infant with such a presentation is wide and includes metabolic disorders (amino acids, lysosomal, mitochondrial), post viral encephalitic sequalae, acute necrotizing encephalopathy of childhood (ANEC), acute demyelinating encephalomyelitis, and epileptic encephalopathies. Autoimmune encephalitis is usually not considered in infants with developmental regression, and the diagnostic workup is directed toward metabolic and neurodegenerative disorders. Our patient fell within the rare spectrum of infantile autoimmune encephalitis cases. A similar case has been previously reported by Ramesh et al.[6] on a six-month-old child from India who presented with seizures, movement disorder, and altered sensorium. The patient also had polymerase chain reaction for herpes simplex virus type 1 DNA (HSV-1 DNA PCR) positivity in CSF. He responded well to immunomodulation. Our patient also responded well to immunomodulation, and on follow-up his movement disorder had subsided and he had regained his milestones. Another case was reported by Patil et al.[7] in a nine-month-old child. The diagnosis and treatment of autoimmune encephalitis in infants is challenging. The presenting symptoms may be non-specific and includes developmental regression, seizures, and movement disorder. MRI brain is frequently normal and EEG may be normal or show non-specific background slowing. The presence of an antecedent febrile illness may be a clue to this diagnosis, but febrile illnesses frequently trigger developmental regression in infants with underlying metabolic or neurodegenerative disorders, bringing them to the notice of physicians. Hence, a high index of suspicion is required to diagnose this disorder in children. There is limited data regarding immunosuppressive treatment of anti-NMDA receptor encephalitis in this extreme age group, especially regarding newer agents like rituximab. As emphasized by Prithvi et al.,[8] immunotherapy in infants presents unique challenges because of immaturity of immune system in this age group, dilemma in administration of vaccines (as it can trigger autoimmunity), and difficulty in assessing response to treatment. Thus, the use of steroids and intravenous (IV) immunoglobulin may be the best option in infants with autoimmune encephalitis. In conclusion, anti-NMDA receptor encephalitis is a rare cause of developmental regression and movement disorder in infants, but it must be suspected and recognised as it is a treatable disease and early therapy may lead to complete improvement. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.