Case Presentation:
A 9‐year‐old previously healthy boy initially presented to an outside hospital with a generalized seizure after one week of subtle behavioral changes and prodromal illness with fever, vomiting, and diarrhea. He had a normal head CT and an EEG with possible epileptiform discharges and was started on Trileptal. He was readmitted two weeks later due to progression of aggressive behavior and psychosis. Cerebrospinal fluid studies were significant for 44 nucleated cells (89% lymphocytes), normal glucose and protein. Extensive testing for an infectious etiology was negative (including negative RMSF Ab, Lyme Disease Ab, Arbovirus panel, enterovirus, HSV PCR), and he was discharged with a working diagnosis of viral encephalitis. He was admitted a third time with periods of unresponsiveness, confusion and staring. MRI/MRV brain was normal, and paraneoplastic and anti‐ N‐menthyl‐D‐aspartate receptor (anti‐NMDAR) studies were sent.
On transfer to our hospital six weeks after the onset of symptoms he continued to exhibit psychotic, hypersexual and disorganized behavior and had another generalized seizure. Further diagnostic workup on transfer was notable for negative Mycoplasma antibodies and paraneoplastic panel, and normal acylcarnitine profile, complement (C3/C4) and CT brain angiogram. The constellation of symptoms of subacute psychosis, hypersexual and disorganized behavior, and seizures was consistent with an autoimmune encephalitis and treatment was initiated with IVIG and pulse‐dose steroids. Anti‐NMDAR antibody subsequently resulted positive. Appropriate surveillance studies were negative for tumor. Rituximab was added to his treatment regimen and he showed steady improvement with return of coherent behavior and language. On discharge the patient was followed by our Neuroimmunology clinic for continued outpatient treatments with IVIG and Rituximab.
Discussion:
Anti‐NMDAR encephalitis is an under‐recognized cause of encephalopathy. Initially discovered in women in association with ovarian teratomas, it has been identified with increasing frequency in recent years. In a recent study the prevalence of Anti‐NMDAR encephalitis was found to be greater than HSV‐1, VZV, or West Nile. It is most prevalent in individuals less than 30 years of age and is often seen without any oncologic association, especially in young males. The clinical progression is marked by a prodromal illness followed by behavioral changes and ultimately neurologic symptoms including seizures and coma. Current treatment involves immunotherapy and results in complete resolution of symptoms in 75% of patients.
Conclusions:
In children who present with encephalopathy, hospitalists should consider anti‐NMDAR encephalitis as a possible etiology among other viral and autoimmune causes. CSF and plasma should be analyzed for the NMDAR antibody. It is important to consider this diagnosis given the rising prevalence and good outcomes with appropriate treatment.