A Teenager with Acute Psychosis in the PICU

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our episode of a 14-year-old girl with sudden acute outbursts of aggression and severe agitation.Here's the case presented by Dr. Damania:A 14-year-old previously healthy teenager with no significant past h/o presents to the PICU with a three-day h/o of aggressive behavior, agitation, and screaming. Her mother reports that her daughter has recently developed insomnia, abnormal movements and is more irritable with temper tantrums and episodic unintelligible verbal output. Parents report no recent stressors at home or at school. She has been also complaining of headaches for the past week along with things "being too loud". She denies any vertigo symptoms or tinnitus. The patient is brought to the ER due to persistent auditory/visual hallucinations followed by agitation, aggressive behavior, and catatonia. There is no h/o of recent illnesses, head trauma, fevers, rash, abdominal pain, diarrhea, or vomiting. Social history is negative for drugs of abuse in the home. Family h/o negative for seizures, and psychiatric disorders.The patient is sent to the ED and upon arrival has an unprovoked convulsive episode concerning a GTC seizure. The patient was initially admitted to the floor but transferred to the PICU for management of severe agitation, aggressive behavior, and fluctuations of blood pressure and heart rate.Initial vitals in the PICU were notable for tachycardia. The patient was found to be afebrile, normotensive for age, and SpO2 96% on RA. Her physical exam though limited by her aggressive behaviors was normal. The heart, lung, and abdominal exams are normal with no rash or bruising on her body.Initials lab work includes a negative:U pregSerum and Urine tox screenCBC, CMP, and UA are all within normal limitsInflammatory markers — including ESR CRP are unremarkable.A head CT which was normal and an A lumbar puncture revealed colorless CSF with 8 white and 0 red cells. Serum and CSF glucose were within normal limits and protein count in CSF was negligible.An extended multi-disciplinary work-up is initiated.To summarize key elements from this case, Rahul this teenage girl has:Sudden outbursts of agitation, and aggressionRecent difficulty in sleepingIrritability, and decreased verbal outputAuditory and visual hallucinationsPotential autonomic dysfunction as she has fluctuating BP and HR All of which brings up a concern for neuropsychiatric symptoms that could be organic in nature.Let's transition into some history and physical exam components of this case?Rahul, what are key history features in the patient presented this case.Seizures, Agitation, and aggressive behavior which could reflect CNS dysfunction are seen in this case.The patient additionally has concern for hallucinations which point to a primary psychiatric disturbance as well. Remember the incidence of new-onset psychosis or schizophrenia in a child <13 is increasingly rare — 1 in 40K and thus identification and thorough workup for an organic cause is increasingly important.Rahul, are there some red-flag symptoms or physical exam components which you could highlight?The physical examination (although limited by her behavior) in this patient is negativeI would particularly stress the need for a detailed neurological and skin exam.For many of the differentials we will discuss, we must evaluate for rashes, changes in nails or hair, bruising or cutting marks in her arms, and even evidence of trauma to the (head and spine), and considering both an abdominal exam to r/o organomegaly as well as bi-manual pelvic exam is important to perform.Pradip, to continue with our case, the patient’s labs were consistent with?Rahul, actually her labs were normal. Besides the CBC, CMP being normal her presentation CRP & ESR were also normal. This was interesting as CRP and ESR are non-specific highly sensitive markers whose elevations may point to an infectious or inflammatory process.Speaking of infection or inflammation, a lumbar puncture was done and her CSF revealed zero red cells but 8 white cells with a normal protein and glucose.Thyroid studies include the presence of serum thyroid (thyroid peroxidase, thyroglobulin) antibodies. All of which were negative.As we continued to observe this patient's behavior in the PICU we expanded our CSF and serum studies. One of the panels which we sent from the CSF and serum was the auto-immune encephalopathy panel. The panel includes various Ab including:Glutamic Acid Decarboxylase (GAD) AbAquaporin-4 Receptor Ab,Gamma-Aminobutyric Acid Receptor, Type B (GABA-B-receptor) Ab, GFAP Ab,Voltage-Gated Potassium Channel (VGKC) Antibody, and many more.One essential Ab that is tested in the panel, which is an important differential in our case and one that has increased in media popularity, is the N-methyl-D-Aspartate Receptor (NMDA receptor) Ab. The book Brain on Fire by Susannah Cahalan published in 2012 and the subsequent movie released in 2016 has brought this diagnosis to the public limelight.OK to summarize, we have a 14-year-old girl with acute onset of neuropsychiatric symptoms and a working diagnosis of autoimmune encephalitis — the topic of our discussion today.Let's start with a short multiple-choice question: A patient presents with new-onset aggression, irritability, and seizures. A diagnosis of Anti-NMDA encephalitis is suspected, the subsequent test to confirm the diagnosis is:A) MRI chest, abdomen, and pelvisB) Serum antibodies against GLUN1 subunit of the NMDARC) CSF antibodies against GLUN1 subunit of the NMDARD) CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)Rahul the correct Answer is C. CSF antibodies against the GLUN1 subunit of the NMDAR. Answer A (MRI chest, abdomen, and pelvis) is not required for an initial diagnosis but make be required for the detection of teratomas (58% of young females have an ovarian teratoma). ( Answer B (Serum antibodies against GLUN1 subunit of the NMDAR) is wrong because of false-negative results in 14% of cases. False-positive serum results can also be seen in patients without anti-NMDA receptor encephalitis. Answer D (CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)) are typically seen in adults with anti-LGI1 encephalitis who have faciobrachial dystonic seizures, memory loss, hyponatremia, and paroxysmal dizzy spells. In our patient antibodies against the GLUN1 subunit of the NMDAR were detected in the CSF and the serum.As you think about our case, Pradip what would be your differentialAcute Demyelinating encephalopathies would be at the top of my differential. These would...