Indian Pediatr 2014;51:
Anti-NMDA Receptor Encephalitis in an
TK Shruthi, S Shuba, PS Rajakumar and *S Chitrambalam
From Departments of Pediatrics and *Neurology, Sri
Ramachandra Medical College, Chennai, Tamil Nadu, India
Correspondence to: Dr TK Shruthi, Assistant
Professor, Department of Pediatrics, SRMC and RI,
Porur, Chennai 600 116, India.
Received: June 28, 2013;
Initial review: July 08, 2013;
Accepted: March 12, 2014.
Background: Anti N-methyl-D-aspartate
(NMDA) receptor encephalitis is an immune mediated disorder. Case
characteristics: A previously healthy 14-year-old girl presenting
with generalized tonic clonic seizures and altered behavior.
Observation: In view of refractory seizures, hallucinations,
psychobehavioral and catalepsy like symptoms, and CSF showing
lymphocytic pleocytosis, possibility of autoimmune encephalitis was
considered. Serum was positive for anti-NMDA receptor antibodies.
Outcome: She recovered completely in six months without any sequelae.
Conclusion: Anti-NMDA receptor encephalitis - a potentially
treatable disease - should be considered in differential diagnosis of
encephalitis when acute behavioral changes, seizures or dyskinesias are
Keywords: Encephalitis, Catalepsy, Psychosis,
Anti–N-methyl-D-aspartate (NMDA) receptor
encephalitis is a disorder of the limbic system that largely affects
children. It is often dismissed initially as a psychiatric syndrome or
viral encephalitis. As this is a potentially treatable disorder, and
occasionally the first indication of an underlying malignancy, prompt
recognition and treatment is critical.
A previously healthy 14-yr-old girl presented to us
with generalized tonic clonic seizures and altered behavior. Two weeks
prior to the admission, she displayed personality changes, memory loss,
psychosis and hallucinations. She was treated with antipsychotics.
On examination, she was drowsy (Glasgow coma scale
11/15), normotensive and euthermic. She was aphasic and not oriented to
person, place or time but was able to localize painful stimulus. She had
involuntary movements in the form of orofacial dyskinesia, pin-rolling
movements, conjugate gaze and oral twitching; lead pipe rigidity and
dystonia were present. Cranial nerves and fundus examination were
normal. A probable diagnosis of viral encephalitis was considered and
she was given empirical ceftriaxone, acyclovir, anticonvulsants and
other supportive treatment.
Routine blood investigations and magnetic resonance
imaging (MRI) of brain were normal. Electroencephalography (ECG) showed
bilateral diffuse dysfunction. CSF examination revealed 1250 cells/hpf
(polymorphs 25%, lympocytes 75%) with protein of 12 mg/dL and sugar 76
mg/dL. Polymerase chain reaction for herpes simplex virus was negative
and bacterial cultures were negative. Subsequently, she developed
refractory status epilepticus needing multiple antiepileptic drugs and
In view of refractory seizures, hallucinations,
psycho-behavioral and catalepsy like symptoms (mute, akinetic,
unresponsive to verbal commands while keeping her eye open), and CSF
showing lymphocytic pleocytosis, possibility of autoimmune encephalitis
was considered. Child was treated with intravenous pulse
methylprednisolone for 5 days, later changed to oral methylprednisolone.
Child’s serum was positive for anti-NMDA receptor antibodies but
negative for anti-glutamate-receptor antibodies, GABA-B-receptor
antibodies, LGi-1 antibodies and CASPR2 antibodies. Abdominal and pelvic
ultrasonography done to screen for ovarian teratoma was unremarkable.
Intravenous immunoglobulin (400 mg/kg/d) was administered for 5 days
following which there was gradual clinical improvement. She was weaned
off ventilator and antiepileptic drugs were tapered. She recovered
gradually and discharged home after three months on oral steroids. At
discharge parents were counseled regarding need for yearly tumor-screening.
She is on regular follow-up and has recovered completely.
Anti-NMDA receptor encephalitis is a disorder
mediated by antibodies to the NR1 subunit of the receptor . Clinical
manifestations include (a) prodromal phase with nonspecific
symptoms like fever, headache and nausea (b) psychotic phase with
emotional disturbances, amnesia, cognitive decline and strange behavior
(c) unresponsive phase with catalepsy like symptoms and athetoid
dystonic posturing (d) hyperkinetic phase with orofacial limb
dyskinesia and orolingual dyskinesia and (e) recovery phase with
gradual or complete recovery. Diagnosis is made by characterstic
clinical features, antibody to NMDA receptors in serum and/or CSF, CSF-pleocytosis,
and EEG showing diffuse delta activity with paroxysmal discharge
(extreme delta brush pattern) . MRI brain FLAIR-sequence at
presentation may be normal or it may demonstrate bilateral medial
temporal lobe hyperintense signals, predominantly involving the
hippocampus. First line therapy includes pulse methyl prednisolone and
intravenous immunoglobulins or plasmapheresis . Second line therapy
includes rituximab, cyclophosphamide or both [1,3,4]. This child was
treated with pulse methylprednisolone and intevenous immunoglobulins.
Anti-NMDA receptor encephalitis was originally
described as a paraneoplastic syndrome, associated with ovarian
teratomas containing neural tissue with antibodies cross reacting to the
NMDA receptor . Approximately 50% of adults and 70% of pediatric
patients who presents with anti-NMDA receptor encephalitis have no
identifiable tumour [1,4]. Ultrasound abdomen was normal in this child.
Armangue, et al.  in a case series of 20
pediatric patients from Spain observed more neurological and less
psychiatric symptoms (67% vs 55%, respectively) at the onset in
children less than 12 yrs, while older children had predominantly
psychiatric symptoms. The child presented here had psychobehavioral
symptoms followed by neurological symptoms.
Anti-NMDA receptor encephalitis is a potentially
treatable disease but does not have uniformly good outcome. Recovery is
usually protracted over months to years. 75% of patients may have
complete or near complete recovery [1,4]. It should be considered in
differential diagnosis of encephalitis when acute behavioral changes,
seizures or dyskinesia are present.
Acknowledgement: Prof. P Ramachandran for his
guidance and support for preparing this manuscript.
Contributors: All the authors were involved in
management of case and writing of manuscript.
Funding: None; Competing interests:
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Hida A, Hanajima R, et al. Response of anti-NMDA receptor
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