​Inflammation and Cytokines Associated With MIA

At present, MIA is rather represented by fluctuations in specific cytokine levels in the maternal serum and how they affect neurodevelopment and predisposition to psychiatric disorders.

All epidemiological human studies dispose of maternal and neonatal plasma that can be tested for cytokine amount along with behavioral and cognitive studies performed on the progeny (for schematic illustration, see Fig. 15.2).

Increased concentrations of proinflammatory cytokines in the maternal serum have been . .  .

​Temporal Stage of Infection and Cytokine Exposure

​The gestational timing at which the infection and immune response occurs is believed to be a regulator of the MIA impact on neurodevelopment.

While Zika virus and Cytomegalovirus infections provide a risk of developing NDDs regardless of the gestational time window, other viral infections have been shown to have a greater risk at specific stages of pregnancy.

Rubella infection poses a higher risk during the first trimester, while Parvovirus and Treponema pallidum poses a higher risk during the

​Modeling MIA: Animal and Human

Human epidemiological studies along with preclinical models indicate that MIA may prime for altered neurodevelopment in susceptible individuals, with possible neuropsychiatric manifestations later in life.

In this section, we will review the most prominent preclinical in vivo and in vitro MIA models (also listed in Table 15.1 with additional studies), summarizing their translational utility in understanding the role of MIA as a potential risk factor for neuropsychiatric conditions of

​Maternal Immune Activation Effect on Neuroglia

As mentioned above, preclinical models revealed that MIA is able to induce fetal brain changes via inflammatory mediators such as cytokines (Smith et al., 2007; Pratt et al., 2013; Schaafsma et al., 2017).

Preclinical MIA models further implicated IL-6 as a potential propagator of the maternal-to-fetal brain inflammatory response (Smith et al., 2007).

Alteration in fetal brain immune functions can have profound consequences for neurodevelopment, as the brain immune system is directly involved

​The COVID-19 Pandemic

Since November 2019, a novel viral pandemic, called coronavirus disease 2019 (COVID-19) and caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), placed pregnant women in a high-risk group.

Meta-analysis studies reported that pregnant women show a more severe COVID-19, manifesting less of the common symptoms such as fever, cough, and dyspnea, but are at higher risk of admission to the intensive care unit, preterm birth, and subsequent admittance into neonatal unit (Allotey et

Conclusions, Speculations, and Future Directions

The susceptibility to infections is strongly linked to MIA, but a genetic component and secondary stressors also play a role, especially in neuropsychiatric disorders with late onset like SCZ (Nudel et al., 2019). It was mentioned above that some studies are focusing on modeling MIA via double-hit models.

Future research should be focusing more on those studies, in which the MIA hit is later on accompanied by a secondary stressor model. The recently introduced use of iPSC-derived human models

Pediatric neuroimmune disorders comprise a heterogeneous group of immune-mediated CNS inflammatory conditions.

Some, such as multiple sclerosis, are well defined by validated diagnostic criteria.

Others, such as anti-NMDA receptor encephalitis, can be diagnosed with detection of specific autoantibodies.

This review addresses neuroimmune disorders that neither feature a diagnosis-defining autoantibody nor meet criteria for a distinct clinicopathologic entity.

A broad differential in these cases should include:
* CNS infection,
*noninflammatory genetic disorders,
*toxic exposures,
*metabolic disturbances, and
​*primary psychiatric disorders.

Neuroimmune considerations addressed in this review include:
* seronegative autoimmune encephalitis,
*seronegative demyelinating disorders such as neuromyelitis optica spectrum disorder, and
*genetic disorders of immune dysregulation or secondary neuroinflammation.

In such cases, we recommend a broad diagnostic workup:
* to support the presence of neuroinflammation,
* exclude non-neuroimmune disorders,
* detect autoantibodies and other biomarkers of known diseases,
* identify any potential genetic drivers of neuroinflammation, and
​*provide case-specific insights into pathophysiologic mechanisms of inappropriate immune pathway activation or dysregulation.

This review includes an extensive list of useful diagnostic tests and potential implications thereof, as well as a proposed algorithm for the diagnosis and management of the pediatric patient with atypical neuroimmune disorders

​No prior work has directly compared the impacts of transcranial photobiomodulation (tPBM) and transcranial magnetic stimulation (TMS) on the human brain. This within-subjects pilot study compares the effects of tPBM and TMS of human somatomotor cortex on brain structural and functional connectivity.  . . .

​​Thus, tPBM may be superior to TMS at inducing changes in connected nodes in the somatomotor cortex, although further research is warranted to explore the potential therapeutic benefits and clinical utility of tPBM.