CHILDREN WITH AE: AN APPROACH TO DIAGNOSIS AND TREATMENT 

JM Paolicchi, MA MD FAAN FAES

​

HOW DO WE CHARACTERIZE SERONEGATIVE AE PATIENTS/HASHIMOTO’S ENCEPHALOPATHY (HE) 

Fortunately, there has recently been a consortium of specialists in pediatric autoimmune disorders who have established criteria for the diagnosis of pediatric AE, outlined in the paper referenced below. 1. The authors describe several categories of children: those with definite antibody-positive pediatric AE, probable antibody-negative AE, and possible pediatric AE. 

 

The criteria focus initially on the presenting symptoms of the child. The diagnosis of AE can be considered if the child presents with more than two of the following clinical features: altered mental status, EEG abnormalities and seizures, focal neurologic deficits, acute developmental regression movement disorders, and new psychiatric symptoms that are not attributed to a preexisting psychiatric condition. 

 

After a thorough evaluation, outlined below, those who have discoverable autoantibodies are classified as Definitive antibody-positive AE.  Probable antibody-negative AE are for those with clinical criteria and evidence of neuroinflammation such as CSF inflammatory changes, MRI features of encephalitis, or findings on a brain biopsy which is not a typical procedure in the evaluation of children with AE. Patients with clinical symptoms but without clinical evidence of neuroinflammation or auto-antibodies, patients are described as possible AE. In this latter category, it is important to ensure that alternative diagnoses are thoroughly considered. 

​

In addition, the researchers describe specific subtypes of AE in childhood. Definitive antibody-positive AE includes anti-NMDAR encephalitis which is the most common pediatric AE. Anti-MOG AE has a specific MRI finding described as demyelination and is accompanied by visual changes, muscular weakness and tightening, and sensory changes. Limbic encephalitis as it is now understood in adult patients, is uncommon in children. Hashimoto encephalopathy (HE) in children is a challenging diagnosis. Patients typically present with seizures, neurocognitive decline, psychiatric manifestations, focal neurologic deficits, and movement disorders.  The presence of thyroid autoantibodies is a hallmark of HE, but even when present, most children have normal thyroid function. Conversely, thyroid autoantibodies can be present in healthy children. 2,3

​

WHAT ARE THE PSYCHIATRIC EFFECTS OF AE

 

The development of psychiatric manifestations in children with AE can be wide-ranging and explosive. These include delusions, hallucinations, behavioral and sleep disturbance, and neurocognitive deterioration. Unfortunately, this same constellation of symptoms is present in psychiatric conditions that are first seen in later childhood and early adolescence such as anxiety disorders, OCD, agitated depression, bipolar disorder, and schizophrenia. What distinguishes children with AE from primary psychiatric conditions are additional symptoms that include autonomic instability, such as heart rate and blood pressure fluctuations, movement disorders other than tics, and seizures. As mentioned below, the comprehensive evaluation of AE patients also demonstrates EEG, CSF, and MRI abnormalities which are less likely to be a feature of patients with primary psychiatric disorders. 

 

A crucial point of treatment, however, is that families often conceptualize psychiatric conditions and AE as either/or in terms of both diagnosis and treatment. Caregivers are concerned about initiating psychotherapy and psychiatric medications before a full diagnosis and the initiation of anti-inflammatory therapy, but treatments are complementary, not exclusive. Children with AE and psychiatric manifestations require both treatments simultaneously to recover from the broad range of conditions associated with AE. Counseling is also required to help the child with AE recover from the disruptions that occur with learning in school, socializing with friends, and attending social functions.

​

Notes: 

1. Celluci T, VanMater H, Graus  T,  et al. Clinical Approach to the Diagnosis of Autoimmune Encephalitis in the Pediatric Patient. Neurol Neuroimmunol Neuroinflamm 2020, 7: e663.

2. Liba Z, Kayserova J, Elisak M, et al. Anti-N-methyl-D- aspartate receptor encephalitis: the clinical course in light of the chemokine and cytokine levels in cerebrospinal fluid.  J Neuroinflammation. 2016; 13 ( 1): 55. 

3. Behrendt V, Krogias C, Reinacher-Schick A, Gold, R, Kleiter I. Bortezomib treatment for patients with anti-N- methyl-d-aspartate receptor encephalitis. JAMA Neurol. 2016; 73(10): 1251-1253.  

​