Evidence ASD involves Neuroinflammation






https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717322/

Relevance of Neuroinflammation and Encephalitis in Autism

. 2015; 9: 519. 


Abstract

In recent years, many studies indicate that children with an autism spectrum disorder (ASD) diagnosis have brain pathology suggestive of ongoing neuroinflammation or encephalitis in different regions of their brains. Evidence of neuroinflammation or encephalitis in ASD includes: microglial and astrocytic activation, a unique and elevated proinflammatory profile of cytokines, and aberrant expression of nuclear factor kappa-light-chain-enhancer of activated B cells. A conservative estimate based on the research suggests that at least 69% of individuals with an ASD diagnosis have microglial activation or neuroinflammation. Encephalitis, which is defined as inflammation of the brain, is medical diagnosis code G04.90 in the International Classification of Disease, 10th revision; however, children with an ASD diagnosis are not generally assessed for a possible medical diagnosis of encephalitis. This is unfortunate because if a child with ASD has neuroinflammation, then treating the underlying brain inflammation could lead to improved outcomes. The purpose of this review of the literature is to examine the evidence of neuroinflammation/encephalitis in those with an ASD diagnosis and to address how a medical diagnosis of encephalitis, when appropriate, could benefit these children by driving more immediate and targeted treatments.

Estimation of the Percentage of Children with an ASD Diagnosis Who are Affected

Thus, based on the available research, a conservative estimate suggests that at least 69% of individuals with an ASD diagnosis have microglial activation or neuroinflammation. However, given the lower number of subjects analyzed in each of the presented studies, this estimate should be considered with care. The actual percentage could conceivably be more or less. For a more accurate estimate, a larger study is needed – one that quantitatively examines multiple regions of the brain for glial activation in concert with an assessment of other markers of activation (e.g., cytokines); this would permit researchers to determine more precisely the frequency/percentage of individuals with an ASD diagnosis who also show microglial activation.

Considering the Possible Forms and Causes of Encephalitis in ASD

Interestingly, neurotoxic effects and neuroinflammation were observed in young Wistar rats that were injected (intracerebroventricularly) with autism sera within hours after birth. According to , the rats injected with the autism sera demonstrated developmental delay and deficits in social communication, interaction, and novelty. The neurobiological changes and the behavioral autistic features were ameliorated by treatment with a ciliary neurotrophic factor (CNTF) small peptide mimetic, Peptide 6 (P6), which is known to have neuroprotective effects ().

From the evidence presented in this section, it may be plausible that encephalitis in ASD has various underlying factors. Importantly, studies which report a regression of patients into an ASD diagnosis following encephalitis include infectious encephalitis, post-infectious or Autoimmune Encephalitis, or purely Autoimmune Encephalitis (such as NMDA Encephalitis; ; ; ; ; ). What the possible external triggers of this inflammatory process in children with autism may be is the subject of the following section.

Discussion

The dramatic rise in ASD began in the 1990s, and in the past two decades, the rates of ASD have increased by 289% (). The sudden and dramatic rise in ASD prevalence has, in some ways, caught the medical community “off guard.” In the midst of the meteoric rise in rates of autism and ASD, significant new research into the physical symptoms has been done. The challenge now is to incorporate this new research about the physical symptoms of autism into the practice of medicine that historically has stereotyped autism as a purely psychiatric disorder. For the benefit of patients, the physical symptoms of autism must be recognized and treated. For children with ASD, particularly those who have begun to regress into ASD and show other signs of neurological regression, testing for encephalitis may be warranted. Particularly, given the documented cases of children with regressive ASD and NMDA Encephalitis who tested positive for anti-NMDA receptor antibodies, routine testing for anti-NMDA receptor antibodies in ASD should be seriously considered. The study by , mentioned earlier, of the child who regressed into autism and recovered from treatment for NMDA, indicates that there is benefit to recognizing the possibility of encephalitis in children with ASD. The delay in incorporating new research findings into medical practice standards is unfortunate because if a diagnosis of autism or ASD were recognized in the medical community as having a possible component of encephalitis that could be tested and treated appropriately, such treatment for encephalitis would likely reduce, and possibly eliminate, ASD symptoms in some children. Future studies should include treatments for neuroinflammation in ASD.

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. 2018; 12: 72.
Published online 2018 Mar 21. doi: 10.3389/fncel.2018.00072
PMCID: PMC5871676
PMID: 29618972
An Inflammation-Centric View of Neurological Disease: Beyond the Neuron















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