A Pediatric Neurology Perspective on Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection and Pediatric Acute-Onset Neuropsychiatric Syndrome

Maternal thyroid autoimmunity associated with acute‐onset neuropsychiatric disorders and global regression in offspring

“…Some of the children had a clinical course compatible with paediatric acute neuropsychiatric syndrome, although this entity (and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) remains controversial and a recent critical review questioned the existence of the entity. 11 Interestingly, of the 18 children (8 index and 10 siblings) born to the eight mothers, there was a higher rate of neurodevelopmental or psychiatric symptoms in the male children, compared to females. This is consistent with male:female ratios in ASD and Tourette syndrome, and, if our hypothesis is true, suggests males are more vulnerable to the environmental effects of immune activation, as has been demonstrated in animal models.…”

“…5,24 We hypothesize that such fetal brain priming (epigenetically or immunologically) provides a plausible explanation for the infection provoked relapsing-remitting course evident in the majority of the cases described in this report, and a different theoretical mechanistic model of what has been called paediatric acute neuropsychiatric syndrome. 11 The speed of deterioration and response to immune therapies was notably faster than that seen in autoantibody-associated disease and seems more compatible with an innate immune disorder or an alternate process such as cell signalling dysfunction. Similarly, we propose that the immunomodulation treatments could be having direct brain effects, by modifying microglia function, altering gene expression, or modifying cell signalling, 25 rather than a 'classic immune suppression' of peripheral immune molecules.…”

“…In three patients who were incapacitated by their symptoms despite conventional therapies, empirical trials of corticosteroids and intravenous immunoglobulin were effective. Some of the children had a clinical course compatible with paediatric acute neuropsychiatric syndrome, although this entity (and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) remains controversial and a recent critical review questioned the existence of the entity …”

“…Ribonucleic acid transcriptomes from the basal ganglia of patients with Tourette syndrome demonstrate upregulation in immune‐related genes consistent with microglial activation, and neuroimaging studies demonstrate microglial activation in adults with OCD, and children with Tourette syndrome and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection . However, these studies have limitations, and further studies are required to explore this hypothesis …”

“…There is a need for biomarkers in mothers and offspring that may help inform the biological process and treatment of putative immune mechanisms, which at the moment is empirical and understandably criticized . However our hypothetical model, based on our clinical observations and other literature, follows the ‘gene plus environment’ model of ASD and associated neurodevelopmental and psychiatric disorders, involving vulnerability genes plus environmental modifiers or exacerbating factors of disease expression, via epigenetic or immunological mechanisms …”