Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors .
In 2013, the Diagnostic and Statistical Manual of Mental Disorders—5th edition (DSM-5) was published, updating the diagnostic criteria for ASD from the previous 4th edition (DSM-IV).
This new definition is intended to be more accurate and works toward diagnosing ASD at an earlier age.
Epidemiology
The World Health Organization (WHO) estimates the international prevalence of ASD at 0.76%; however, this only accounts for approximately 16% of the global child population .
The Centers for Disease Control and Prevention (CDC) estimates about 1.68% of United States (US) children aged 8 years (or 1 in 59 children) are diagnosed with ASD.
In the US, parent-reported ASD diagnoses in 2016 averaged slightly higher at 2.5%
The prevalence of ASD in the US more than doubled between 2000–2002 and 2010–2012 according to Autism and Developmental Disabilities Monitoring Network (ADDM) estimates.
ASD occurs in all racial, ethnic, and socioeconomic groups, but its diagnosis is far from uniform across these groups.
ASD is more common in males but in a recent meta-analysis, true male-to-female ratio is closer to 3:1 than the previously reported 4:1, though this study was not done using the DSM-5 criteria.
This study also suggested that girls who meet criteria for ASD are at higher risk of not receiving a clinical diagnosis.
The female autism phenotype may play a role in girls being misdiagnosed, diagnosed later, or overlooked. Not only are females less likely to present with overt symptoms, they are more likely to mask their social deficits through a process called “camouflaging”, further hindering a timely diagnosis . Likewise, gender biases and stereotypes of ASD as a male disorder could also hamper diagnoses in girls.
Several genetic diagnoses have an increased rate of co-occurring ASD compared to the average population, including fragile X, tuberous sclerosis, Down syndrome, Rett syndrome, among others; however, these known genetic disorders account for a very small amount of overall ASD cases.
Other risk factors for ASD include increased parental age and prematurity.
Causes
ASD is a neurobiological disorder influenced by both genetic and environmental factors affecting the developing brain. Ongoing research continues to deepen our understanding of potential etiologic mechanisms in ASD, but currently no single unifying cause has been elucidated.
Neuropathologic studies are limited, but have revealed differences in cerebellar architecture and connectivity, limbic system abnormalities, and frontal and temporal lobe cortical alterations, along with other subtle malformations.
A small explorative study of neocortical architecture from young children revealed focal disruption of cortical laminar architecture in the majority of subjects, suggesting problems with cortical layer formation and neuronal differentiation.
Genetic factors play a role in ASD susceptibility, with siblings of patients with ASD carrying an increased risk of diagnosis when compared to population norms, and a much higher, although not absolute, concordance of autism diagnosis in monozygotic twins.
Potential “networks” of ASD genetic risk convergence include pathways involved in neurotransmission and neuroinflammation.
Despite the hysteria surrounding the now retracted Lancet article first published in 1998, there is no evidence that vaccines, thimerosal, or mercury is associated with ASD (68-70)
In the largest single study to date, there was not an increased risk after measles/mumps/rubella (MMR) vaccination in a nationwide cohort study of Danish children.
Ultimately, research continues to reveal factors that correlate with ASD risk, but no causal determinations have been made. This leaves much room for discovery with investigators continuing to elucidate new variants conveying genetic risk, or new environmental correlates that require further study.
Evaluation
Evaluation in ASD begins with screening of the general pediatric population to identify children at-risk or demonstrating signs suggestive of ASD, following which a diagnostic evaluation is recommended.
The American Academy of Pediatrics (AAP) guidelines recommend developmental surveillance at 9, 15 and 30 months well child visits and autism specific screening at 18 months and again at 24 or 30 months.
Early red flags for ASD include poor eye contact, poor response to name, lack of showing and sharing, no gesturing by 12 months, and loss of language or social skills.
Red flags in preschoolers may include limited pretend play, odd or intensely focused interests, and rigidity.
Clinicians should additionally refer the child to a specialist (pediatric neurologist, developmental-behavioral pediatrician, child psychiatrist, licensed child psychologist) for a definitive diagnosis and comprehensive assessment .
A comprehensive assessment should include a complete physical exam, including assessment for dysmorphic features, a full neurologic examination with head circumference, and a Wood’s lamp examination of the skin.
A parent interview, collection of any outside informant observations, and a direct clinician observation of the child’s current cognitive, language, and adaptive functioning by a clinician experienced with ASD should be components of this comprehensive assessment.
The Autism Clinical Spectrum
Additionally, primary care clinicians need to be aware of (and evaluate for) potential co-occurring conditions in children with ASD. According to a surveillance study of over 2,000 children with ASD, 83% had an additional developmental diagnosis, 10% had at least one psychiatric diagnosis, and 16% at least one neurologic diagnosis.
Other common co-occurring medical conditions include gastrointestinal (GI) disorders, including dietary restrictions and food selectivity, sleep disorders, obesity, and seizures.
Other behavioral or psychiatric co-occurring conditions in ASD include anxiety, attention deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder, and mood disorders or other disruptive behavior disorders.
Currently no clear ASD biomarkers or diagnostic measures exist, and the diagnosis is made based on fulfillment of descriptive criteria.
In light of a relatively high yield in patients with ASD, clinical genetic testing is recommended and can provide information regarding medical interventions or work up that might be necessary and help with family planning.
Aside from genetic testing, no other laboratory work up is routinely recommended for every patient with a diagnosis of ASD.
However, further evaluation may be appropriate for patients with particular findings or risk factors.
Neuroimaging is not routinely recommended for every patient with ASD, but may be appropriate.
In patients with a suspicion for TSC or other neurocutaneous disorders, microcephaly, or an abnormal neurologic exam (spasticity, severe hypotonia, unilateral findings).
Patients with suspected seizures should have an electroencephalography (EEG) obtained.
Effects of Low-Level Laser Therapy in Autism Spectrum Disorder
A significant literature exists on the ability of low-level light therapy (LLLT) to penetrate the skull. Low-energy light passes the skull and a therapeutic effect likely exists.
LLLT systems employ the so-called quantum optically induced transparency effect (Scherman et al. 2012; Weis et al. 2010).
This effect controls optical properties of dense media enhancing transparency contrast by a factor of five. Therefore, the skull, spine, or joints can be penetrated even with moderate intensity light reaching deep layers in muscles, connective tissue, and even bone, enabling transcranial effects of LLLT (Hamblin 2018; Hiwaki and Miyaguchi 2018; Grover Jr et al. 2017; de Taboada et al. 2006).
LLLT achieves a therapeutic effect by employing non-ionizing light, including lasers, light-emitting diodes, or broadband light in the visible red (600–700 nm) and near-infrared (780–1100 nm) spectra (Shanks and Leisman 2018; deFreitas and Hamblin 2016).
LLLT is a non-thermal process occurring when a chromophore is exposed to a suitable wavelength of light. Chromophores are responsible for the color associated with biological compounds such as hemoglobin and cytochromes (Cotler et al. 2015).
With chromophore absorption of a photon of light, an electron transits to an excited state, with a physiologic effect occurring when photons dissociate the inhibitory signaling molecule nitric oxide (NO) from cytochrome-C-oxidase, increasing the electron transport, mitochondrial membrane potentials, and production of mitochondrial products such as ATP and NADH (deFreitas and Hamblin 2016; Wang et al. 2016, 2015).
Other effects include the production of reactive oxygen species (ROS) which activate transcription factors, leading to the cellular proliferation and migration (Farivar et al. 2014).
There is a well-established literature on photobiomodulation, supporting improvement in dysfunctional neuronal activity with the use of low intensity red and near-infrared (NIR) light.
Further, low-level light energy has been found safe for humans in the stroke studies, providing a high benefit-to-risk ratio, with no reported side effects of LLLT.
Altered functional connectivity, i.e., synchronous brain activity, might be associated with the deficits characteristically found in ASD (Machado et al. 2015).
Of specific importance is the integrity of functional connectivity in the default mode network (DMN), a network active during inactive resting states, and in cognitive functions linked to the ASD-related social dysfunction.
LLLT promotes cell and neuronal repair (Dawood and Salman 2013) and brain network rearrangement (Erlicher et al. 2002) in many neurologic disorders identified with lesions in the hubs of default mode networks (Buckner et al. 2008).
LLLT facilitates a fast-track wound healing (Dawood and Salman 2013) as mitochondria respond to light in the red and near-infrared spectrum (Quirk and Whelan 2011). On the other hand, Erlicher et al. (2002) have demonstrated that weak light directs the leading edge of growth cones of a nerve.
Therefore, when a light beam is positioned in front of a nerve’s leading edge, the neuron will move in the direction of the light and grow in length (Black et al. 2013; Quirk and Whelan 2011).
Nerve cells appear to thrive and grow in the presence of low-energy light, and we think that the effect seen here is associated with the rearrangement of connectivity.
Reports are now emerging that LLLT and photobiomodulation significantly upregulate brain-derived neurotrophic factor (BDNF), a factor highly associated with dendritic sprouting, neuroplasticity, and brain (Hamblin 2018).
Research on photobiomodulation reveals the beneficial effects of LLLT for a rapidly expanding list of conditions, making this method increasingly accepted by the mainstream medicine.
Experience using PBMT, in ASD
My personal experience with patients with ASD, on Photobiomodulation therapy, have shown improvements in speech, language, comprehension, concentration, social interaction, mood, behaviour and well and co-ordination.
Improvements objectively seen in the ABC checklist, and Clinical Global Impression (CGI) scales, over time.
Gerry Leisman, Calixto Machado, Yanin Machado, and Mauricio Chinchilla-Acosta
The study examined the efficacy of low-level laser therapy, a form of photobiomodulation, for the treatment of irritability associated with autistic spectrum disorder in children and adolescents aged 5–17 years. Twenty-one of the 40 participants received eight 5-min procedures administered to the base of the skull and temporal areas across a 4-week period (test, i.e., active treatment participants).
All the participants were evaluated with the Aberrant Behavior Checklist (ABC), with the global scale and five subscales (irritability/agitation, lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech), and the Clinical Global Impressions (CGI) Scale including a severity of- illness scale (CGI-S) and a global improvement/ change scale (CGI-C).
The evaluation took place at baseline, week 2 (interim), week 4 (endpoint), and week 8 (post procedure) of the study. The adjusted mean difference in the baseline to study endpoint change in the ABC irritability subscale score between test and placebo participants was _15. in favor of the test procedure group.
ANCOVA analysis found this difference to be statistically significant (F ¼ 99.34, p < 0.0001) compared to the baseline ABC irritability subscale score.
The study found that low-level laser therapy could be an effective tool for reducing irritability and other symptoms and behaviors associated with the autistic spectrum disorder in children and adolescents, with positive changes maintained and augmented over time.
In this paper, we present the results of the 6 months follow up assessment, and we demonstrated that improvement in symptoms continued after 6 months following completion of the LLLT procedure for autistics initially randomized to the active (test) group, with no change at all for placebo subjects.
We suggest that LLLT progressively rearranges those neuronal networks related to the complex symptoms in autistics.
Therefore, we can suggest that our results presented in this study showing that clinical improvement of the key evaluable behaviors characteristic of autism disorder in children and adolescents, in symptoms for up to 6 months after following treatment completion, might be patho-physiologically supported with the fact that LLLT progressively rearrange anatomical, functional and effective connectivity, modifying those neuronal networks related to the complex symptoms in autistics, characterized clinically by language impairment, dysfunction in social engagement, stereotypical movements and behaviors, and various and varied cognitive deficits.(Leisman et al. 2018; Machado, Estevez, et al. 2015; Machado et al. 2017; Machado, Rodriguez, et al. 2015)
We conclude that LLLT is a promising and non-invasive tool to treat ASD patients, offering the possibility of clinical improvements in a syndrome where current treatment methods are scarce and not effective.
Children 2022, 9(5), 755;
Published : 20 May 2022
(This article belongs to the Special Issue Child Neuropsychiatry)
tPBM represents a promising intervention for children and adolescents with ASD, considering also its practicality and the freedom of movement it offers.
If other studies will confirm our findings, tPBM could represent a promising device for moving forward to a more precision medicine approach, on the road to personalized treatment in the realm of neurodevelopmental disorders.
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