The Evolving Role of Neurologists in Autism Diagnosis and Management

Autism spectrum disorder (ASD) is a set of related and complex neurodevelopmental disorders characterized by persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior.¹ “Autism is a human intellectual construct with recognizable symptoms,” explains Joshua Rotenberg, MD, child and adolescent neurologist at Houston Specialty Clinic in Texas. “Saying someone has autism is like saying someone has flu-like-symptoms, which could have been caused by Rhinovirus, COVID or any pathogen. Likewise, autism is a recognizable common pathway for many neuro-genetic disorders.”

ASD is one of the most common neurological disorders of early childhood, with 1 in 44 8-year-old children being identified with the condition, according to the estimates from the Centers for Disease Control and Prevention.² Genetic susceptibility to ASD is apparent in the fact that siblings carry a significantly higher risk of ASD diagnosis. Twin studies have revealed a 60% concordance rate for ASD diagnosis in monozygotic twins.³ Moreover, prenatal, perinatal, and postnatal environmental characteristics have been shown to modulate ASD diagnosis and inheritability.

Understanding the Neurological Basis of ASD

In addition to the genetic and environmental link, the neurobiological basis of ASD has been the focus of research for decades. Significant neural, structural, functional, molecular, endocrine, electrophysiological, connective and neurotransmission differences have been recorded between the ASD brain and the neurotypical population.⁴

Some children with ASD, aged 2-5 years old, show abnormal brain overgrowth in regions of the brain associated with cognition and pragmatism, as well as social, emotional, and language functions.⁵ Increased cerebellar volume, amygdala enlargement, and other volumetric abnormalities have been associated with worse social, communication and behavioral outcomes in patients with ASD.

Although the rate of brain development normalizes through adolescence and adulthood,cortical atrophy and reduced amygdala and frontal cortex volume have been detected in some patients with ASD. Dysfunctions in neural networks, distorted inter-hemispheric function, and mitochondrial abnormalities have also been detected. As a result, the current understanding is that ASD is underlined by complex and multi-modal structural and functional neurological abnormalities.⁶

How Neurologists Are Helping to Facilitate an ASD Diagnosis

“Neurologists play a crucial role in the diagnosis of autism,” explains Deepa Menon, MD, assistant medical director, at the Center for Autism & Related Disorders at Kennedy Krieger Institute in Baltimore, Maryland. “This includes the evaluation and management of autism-related comorbidities.”

“We help manage any illness experiences of autism,” adds Dr Rotenberg. “Our primary role is in facilitating a more specific diagnosis of ASD. However, we also assist with genetic testing and help the patient’s families understand the actionable medical information that comes from it. Neurologists should also be there to help families understand the disorder, particularly the cognitive processing. This can be very difficult for many families.”

Neurologists typically carry out an evaluation of symptoms associated with the ASD triad, as defined by the DSM criteria. “The DSM criteria is the baseline for ASD diagnosis. Furthermore, insurance companies often require standardized testing such as the autism diagnostic and observation scale (ADOS). These baseline metrics help analyze improvement over time,” explains Dr Rotenberg.

Neurologists also utilize motor skills in their diagnostic criteria, as these are quantifiable and can be objectively measured. Diverse motor deficits in both gross and fine motor domains such as gait, postural control and coordination have been recorded in ASD.⁷ Repetitive behaviors, a type of motor deficit, can also be identified in children using validated scales. In children with high functioning autism, praxis examination can help assess impairments in skilled movements.

The goal of the neurological evaluation is to rule out any associated neurological disorders. Although additional laboratory tests, metabolic work-ups or neuroimaging tests are not routinely recommended, they may be carried out when patients present with concerning symptoms. For example, electroencephalograms (EEGs) are particularly beneficial in determining the risk of seizures in patients with ASD. Subclinical EEG abnormalities in seizure-free ASD patients have also been associated with lower intellectual functioning and motor dysfunctions.⁸

“Every child with autism does not need a prolonged EEG,” Dr Menon. In addition to the expense, an EEG process can be traumatic. The prevalence of EEG abnormalities without seizures is high, and an abnormal test can create deep anxiety and medicalize a child.

Following initial consultation by a physician, children or adults with ASD are evaluated by multi-specialist teams to arrive at a definitive diagnosis. “At our center I am fortunate to work with speech/occupational therapists, neuropsychologists, social work/care coordinators and behavioral therapists,” says Dr Menon.

Common Neurological Comorbidities in ASD

“Autism is associated with diverse comorbid neurological disorders, including seizures, sleep disorders, and possible developmental regression. Neurologists can help with the early detection and management of these conditions,” explains Dr Menon.

According to statistics:

• At least 30% of patients with ASD are also diagnosed with epilepsy. The ASD brain is more prone to seizures owing to a lower seizure threshold believed to result from a combination of environmental and genetic factors. Although no single seizure type is more prevalent in ASD, these often co-present with cognitive impairments.⁹
• Intellectual disabilities are the most common comorbidity associated with ASD, affecting 80% of ASD patients.¹⁰
• Sleep disorders, particularly insomnia, are recorded in 44-83% of patients with ASD, typically toddlers. This is believed to result from a melatonin deficiency in the ASD brain.¹¹

Other co-occurring disorders include gastrointestinal disorders, anxiety, attention deficit hyperactivity disorder, obsessive compulsive disorder, and mood disorders. Advances in genetic testing have helped elucidate polygenic causative genes common to ASD and other neurological disorders, suggesting a shared genetic basis for these disorders:

“Children with developmental regression have a much higher risk of abnormalities. Yet, the recognition is low, leading to delayed referrals. EEGs showing signs of developmental encephalopathy can facilitate early treatment with seizure medications,” adds Dr Rotenberg.

Exploring ASD Treatment Options

With no pharmaceutical agents approved for the treatment of ASD, treatment strategies primarily focus on behavioral therapies. Early immersive behavioral interventions and social training can significantly enhance social development and interactions. “It is well recognized that social skills improve when sleep disorders are treated. Conversely, insomnia is a common reason why many children with autism are institutionalized,” notes Dr Rotenberg.

To this end, early diagnosis of children with ASD by neurologists can help kick start early management and thus unlock better prognosis. Additionally, a thorough evaluation by neurologists can help detect risks or early signs of comorbid neurological disorders such as seizures, enabling physicians to act preemptively.

Some novel therapeutic modalities have also been explored for ASD management. For example, repetitive transcranial magnetic stimulation (rTMS) has been successfully utilized to restructure cortical excitability of neurons in the inferior parietal lobule, thus enhancing social cognition, emotion, empathy, memory, speech and action planning.¹² Mente devices that provide non-invasive neurofeedback have been shown to enact significant changes in brain activity, sensory-motor behavior and repetitive behaviour.¹³ Cannabidiol (CBD) enriched cannabis has also shown promise in treating children with mild autism symptoms.¹⁴

As advances in genetic and neuro-imaging techniques help shed light on the neurobiological basis of ASD, neurologists are likely to become even more critical to building strategic diagnostic models for patients with ASD.

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Publishing; 2013.
2. Centers for Disease Control and Prevention. Autism and Developmental Disabilities Monitoring. Updated March 31, 2022. Accessed April 11, 2022. https://www.cdc.gov/ncbddd/autism/addm.html
3. Frazier TW, Thompson L, Youngstrom EA, et al. A Twin Study of Heritable and Shared Environmental Contributions to Autism. J Autism Dev Disord. Published online March 7, 2014. doi:10.1007/s10803-014-2081-2
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7. Gandotra A, Kotyuk E, Szekely A, Kasos K, Csirmaz L, Cserjesi R. Fundamental movement skills in children with autism spectrum disorder: A systematic review. Research in Autism Spectrum Disorders. 2020;78:101632.
8. Precenzano F, Parisi L, Lanzara V, et al. Electroencephalographic Abnormalities in Autism Spectrum Disorder: Characteristics and Therapeutic Implications. Medicina (Kaunas). Published online April 19, 2020. https://doi.org/10.3390/medicina56090419
9. Lukmanji S, Manji SA, Kadhim S, et al. The co-occurrence of epilepsy and autism: A systematic review. Epilepsy & Behavior. Published online August 6, 2019. https://doi.org/10.1016/j.yebeh.2019.07.037
10. Srivastava AK, Schwartz CE. Intellectual Disability and Autism Spectrum Disorders: Causal Genes and Molecular Mechanisms. Neurosci Biobehav Rev. Published online April 4, 2014. doi:10.1016/j.neubiorev.2014.02.015
11. Mazzone L, Postorino V, Siracusano M, Riccioni A, Curatolo P. The Relationship between Sleep Problems, Neurobiological Alterations, Core Symptoms of Autism Spectrum Disorder, and Psychiatric Comorbidities. J Clin Med. Published online May 3, 2018. doi:10.3390/jcm7050102
12. Yang Y, Wang H, Xue Q, Huang Z, Wang Y. High-Frequency Repetitive Transcranial Magnetic Stimulation Applied to the Parietal Cortex for Low-Functioning Children with Autism Spectrum Disorder: A Case Series. Frontiers in Psychiatry. Published online May 9, 2019. https://doi.org/10.3389/fpsyt.2019.00293
13. Carrick FR, Pagnacco G, Hankir A, et al. The Treatment of Autism Spectrum Disorder with Auditory Neurofeedback: A Randomized Placebo Controlled Trial Using the Mente Autism Device. Frontiers in Neurology. Published online July 5, 2018. https://doi.org/10.3389/fneur.2018.00537
14. Bilge S, Ekici B. CBD-enriched cannabis for autism spectrum disorder: an experience of a single center in Turkey and reviews of the literature. J Cannabis Res. Published online December 16, 2021. https://doi.org/10.1186/s42238-021-00108-7