Cahalans-Month-of-Madness/

Autoimmune Encephalitis William Gallentine, DO Assistant Professor, Pediatrics – Division of Child Neurology Heather Van Mater, MD MS Assistant Professor, Pediatric Rheumatology Xavier Preud’homme, MD Assistant Professor, Internal Medicine & Psychiatry

Clinical Features of Patients with anti- NMDAR encephalitis at 1 month (n=577) Titulaer MJ et al. Lancet Neurol 2013; 12:157-65

May mimic psychiatric disorders Patients with NMDAR encephalitis (as well as many other types of autoimmune encephalitis) most commonly present with psychiatric symptoms which may mimic common disorders like schizophrenia and bipolar disease

Psychiatric symptoms presenting along with symptoms inconsistent with primary psychiatric diagnosis The presence of non-psychiatric signs such as seizures, movement disorder, cognitive impairment, language loss, or decreased level of consciousness should serve as red flags indicating further evaluation

Recommended Workup At the outset (DO NOT HAVE TO WAIT FOR NEUROLOGY CONSULT!!) Serum inflammatory markers (ESR, CRP) Serum autoantibodies (NMDAR and paraneoplastic, thyroid) MRI with and without contrast EEG Strongly consider lumbar puncture CSF autoantibodies (NMDAR and paraneoplastic) OP, cell count, glucose, protein, oligoclonal bands

Take home points Providers should have a low threshold for further evaluation for these disorders Because autoimmune encephalitis is highly responsive to immunotherapy (especially IF TREATED EARLY in the course!!).

Treatments The cornerstone of treatment is immunomodulatory therapy Steroids Plasmapheresis IV immunoglobulin (IVIG) Oral immunosuppressents including Cellcept Rituximab Cyclophosphomide (Cytoxan) Removal of tumors – for example, ovarian teratoma in anti-NMDAR encephalitis Management of symptoms while waiting for immunomodulatory therapy to work (e.g., for seizures, agitation)

Prognosis of anti-NMDAR encephalitis 6% mortality 81% had good outcome at 24 month f/u Initial signs of improvement 4 weeks in 53% In non-responders to 1 st line therapy, only 57% received 2 nd line therapy, even though 2 nd and 3 rd line immunotherapy resulted in significantly better outcomes Relapses: 12% relapse risk in 2 years 2/3 of relapses less severe than initial Those that received 2 nd tier agent on initial presentation had fewer relapses Predictors of good outcome: Early treatment For first-line failures, administration of 2 nd line agent Titulaer MJ et al. Lancet Neurol 2013;12:157-65

Take Home Points Initiate treatment as soon as possible Recovery occurs over months Average of 14 months for anti- NMDAR encephalitis If first line treatment fails, move to second line treatment

Overcoming Our Cognitive Biases ESSENTIALISM This is medical so it is not psychiatric… or This is purely behavioral… Must recognize and manage the cluster of signs constituting catatonia Agitation, inappropriate laughter or crying, enuresis, drooling, movement disorder, autonomic instability, etc. Benzodiazepine (Ativan) rather than antipsychotics CURSE of KNOWLEDGE If it is catatonia then it is a psychiatric disorder STEREOTYPICAL BIAS Young female must be psychiatric… Positive Family history of psych D/O must be same

A Call to Action Listen to patients, listen to parents Evaluation and treatment requires multidisciplinary teams Support Dr. Gallentine and Dr. Van Mater’s Duke Children’s Autoimmune Brain Disease Program to be a Center of Excellence for the treatment of autoimmune encephalitis Develop a similar Duke program for adults We have founded the Autoimmune Encephalitis Alliance and are launching a Autoimmune Encephalitis Centers of Excellence Campaign to Establish clinical standards of care across medical disciplines Coordinate basic and clinical research efforts Raise awareness / connect families so nobody faces autoimmune encephalitis alone First fund raising event: Florence Forth – Fundraising Run, March 2, Information at: