Young girl with abnormal behavior: Anti-N-Methyl-D-Aspartate receptor immune encephalitis
A 17-year-old, school-going girl developed acute onset of behavioral change, initially manifested as extreme politeness and obedience (as against her pre-morbid gregarious personality), progressing within a few days to excessive and irrelevant talks accompanied with features of disinhibition. Frank psychotic features emerged within 10 days, including verbal and physical aggression, muttering to herself, and marked delusional thoughts with a tendency to run amok. A diagnosis of acute functional psychosis was made by a psychiatrist and oleanzapine was started. The behavioral syndrome persisted, albeit with mild reduction of psychomotor activity. After a few days, she developed stiffness of whole body along with akinesia and mutism. She was evaluated further by neurologist and psychiatrist. Magnetic resonance imaging (MRI) Brain revealed few scattered, non-diffusion restricted, non-contrast-enhancing T2 and Fluid Attenuated Inversion Recovery sequence (FLAIR) hyper intensities in periventricular and centrum semi-ovale region. Cerebrospinal fluid (CSF) examination revealed no cells, normal protein, and normal glucose levels. CSF viral markers, Venereal Diseases Research Laboratory test, gram stain, acid fast bacillus stain, India ink, cryptococcal antigen, and bacterial, mycobacterial and fungal cultures were negative. Electroencephalogram showed a non-specific diffuse theta delta slowing. She had low grade fever and serum Creatinine Phosphokinase was raised to 1800 U/dl. A diagnosis of NMS due to oleanzapine was considered and dantrolene and hydration were started. Other than a slight reduction of rigidity, no other improvement was noticed. Clinical worsening continued over next 2 weeks, with increasing mental obtundation and persistent akinetic mute state. About 4 weeks after disease onset, frequent bouts of tachypnea, tachycardia, hypotension, and sweating were noticed, which deteriorated over next 48 h to gasping for breath, associated with oxygen desaturation in blood, necessitating endotracheal intubation, and mechanical ventilation. At this stage, patient was brought to our center. Widely fluctuating heart rate and blood pressure were noted, with stimulus-induced sinus tachycardia, tachypnea, and diaphoresis, necessitating sedative infusion. A provisional diagnosis of sepsis syndrome due to bilateral aspiration pneumonia was considered by the treating physician. She received critical care and medical support and was re-evaluated by neurology team for her underlying progressive illness. A possibility of immune encephalitis was considered at this stage. MRI Brain was repeated; similar changes as noted before were found []. Besides work up for infectious meningoencephalitis (which turned out normal again), CSF samples were also sent for anti-NMDA receptor antibody, anti-Voltage gated potassium channel VGKC, and anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antibody levels. Vasculitic work up (anti nuclear antibody, anti-double stranded DNA, anti phospholipid antibody, lupus anti-coagulant, cytoplasmic and perinuclear anti neutrophilic cytoplasmic antibody) was normal. Anti-thyroid peroxidase antibody and anti-thyroglobulin antibody were negative. Computed tomography (CT) scan of chest, abdomen, and pelvis revealed neither ovarian teratoma nor any other malignancy. Patient had two episodes of tonic-clonic seizures, unrelated to any transient metabolic abnormality. While the immune CSF markers were still awaited, it was thought prudent to empirically treat her with immunomodution. She received intravenous immunoglobulin (IVIG), 20 g/day, for 5 days. Within a few days, first signs of improvement of sensorium were noticed with ability to spontaneously open eyes and fixate gaze. The clinical course was further complicated by sequential development of ventilator-associated bilateral pneumothorax, on right side followed by left, necessitating bilateral intercostal tube drainage. During the stage of improvement of sensorium, she developed severe oro-lingual dyskinesias which subsided over next 10 days. Patient was gradually weaned off the ventilator within 2 weeks after receiving IVIG. The anti-NMDA antibody in CSF was meanwhile reported to be positive, whereas anti-VGKC and anti-AMPA antibodies were negative, thus confirming the diagnosis of anti-NMDARE. The patient had a remarkable and quick neurological recovery, with full recovery of sensorium with normal higher mental functions, within 4 weeks of receiving IVIG, with subtle, steadily resolving distal acral lower motor neuron deficit due to overlap of critical illness polyneuropathy. The need for follow-up and periodic screening for teratoma has been explained to the patient and her parents.