Brain MRI in Children with Autism Spectrum Disorder

Introduction

Autism spectrum disorder (ASD) is a neuro-developmental disorder with early childhood onset, and characterized by restricted and repetitive behaviors along with difficulty in social communication and social interaction ^{[1, 2]}

Globally, the prevalence is 100/10,000, with a 4:1 male predominance. In Egypt, community based countrywide screening revealed an estimated 3.3% of 41,640 children aged 1 to 12 had ASD. Main Types of ASD according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) include Autistic disorder, Asperger’s Syndrome, Childhood Disintegrative Disorder (CDD), Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). ^{[3, 4, 5, 6]}

Numerous non-invasive imaging techniques have been developed for the early identification of ASD characteristics. Brain magnetic resonance imaging (MRI) is a useful method for investigating brain structural changes in children with ASD. There is no general conse-nsus on specific neuroimaging features of autism; however, magnetic resonance imaging methods have been helpful in evaluating small structural abnormalities and variants in order to better understand the neuro-pathophysiology of ASD.^[7]

Patients and Methods

This study included 50 pediatric patients diagnosed with ASD (classic type) according to DSM-5 diagnostic criteria, they had regular follow up visit to Pediatric Neuropsychiatric

Clinic at Minia University Children Hospital, from January 2023 to January 2024.

Ethical Considerations:

The aim and nature of this study was explained for each parent before participating in the study. Before participants were enrolled, parents gave their informed consent, which allowed them to withdraw from the study avoiding using deceptive practice. This study also was approved by Pediatric Department Council and had approval of the ethical committee of Faculty of Medicine, Minia University No 718:4/2023.

Children aged 4-16 years old with a confirmed diagnosis with autism according to DSM-5 diagnostic criteria were included in this study, ^[5,6] while children with any systemic diseases, neuro-logical diseases, other psychiatric disorders, and patients who refuse to participate in this study were excluded from this study.

All patients were subjected to:

- Complete medical history, through general and neurological examination

- Evaluation of autism symptoms severity by Gilliam Autism Rating Scale–Third Edition (GARS-3). ^{[8, 9]}

- Brain imaging using 3Tesla MRI brain diffusion.

1. Careful history taking included:

Name, age, sex, residency, symptoms and additional data were collected from parents included: Social isolation, interaction, stereotyping movements, hypo/ hyperactivity, motor and sensory symptoms.

Perinatal history  of maternal previous abortion, consanguinity, drugs, birth order, and the condition of other siblings.

2. Thorugh clinical examination.
3. Evaluation of autism symptoms severity: by The Gilliam Autism Rating Scale–Third Edition (GARS-3) ^{[8, 9]}
4. Brain imaging using 3T MRI brain diffusion scanning machine : the brain images were assessed independently and evaluated by two expert pediatric neuro-radiologist through double blind technique, and their final findings were reported in this study, they assess brain radiological mor-phology, technical parameters (thickness, TE, TR) were set up to obtain high quality morphological sequencing (T1, T2, FLAIR T2 weight) images mainly that provide adequate anatomical details and high contrast between tissues.

Results

As shown in table (1), there are 16% of autistic children had delayed motor development, 84% had delayed mental development, 52% had sleep disorder. 32% of the studied autistic children not receive medical treatment for the comorbid symptoms of autism (aggressive behavior and sleep disorder), while 44% were on atypical antipsychotic treatment (Risperidone, Aripiprazole), and 24% were on Atomoxetine.

As shown in table (2), mean GARS-3 autism index 106±13.5 and mean GARS-3 raw total score 32.7 ± 6.2, divided into the following subscales; GARS-3 social interaction with mean score 11±3, GARS-3 communication with mean score 10.6±3.2 and GARS-3 stereotyping with mean score 11±3.

As regard MRI findings in studied autistic children (table 3), 54% of autistic children had normal brain MRI, 12% had benign enlargement of the subarachnoid space and persistent cavum septum pellucidum (for each item separately), 8% had faint periventricular faint white matter signal intensity, 6% had ictatic ventricles and 4% had Mega cisterna magna and thin corpus callosum (for each item separately).

GARS-3 total raw score, GARS-3 social interaction score and GARS-3 communication score were significantly higher in autistic children with Mega cisterna magna (mean ± SD= 43.5±0.7 m 17±0 and 16±0 respectively) than in other findings. As regard stereotyping score, mean was significantly higher in cases with benign enlargement of the subarachnoid space finding in MRI (mean±SD= 14.6±1.8) than in other brain MRI finding.

Discussion

The aim of this study was to evaluate the role of brain MRI in pediatric patients diagnosed with ASD.

This study showed that 54% of studied autistic children had normal brain MRI, and the most frequent radiological variants recorded in studied patients were benign enlargement of the subarachnoid space and persistent cavum septum pellucidum.

These results were in agreement with Rochat et al., (2020) who found that mega cisterna magna, ventricular malformations, and aberrant white matter signal intensity as important incidental findings (IFs) in ASD. Children and adolescents with ASD have a higher prevalence of IFs, which may indicate that neural maldevelopment underlying the ASD, abnormal cortical development, atrophy, corpus callosum anomalies, ventricular anomalies, and mega cisterna magna were among the MRI abnormalities seen in children diagnosed with ASD.^[10]

This study was in correspondence with Erbetta et al., (2015) who showed that abnormal brain

MRI was in 44% of autistic group, Mega cisterna magna was the primary finding of the brain MRI. These abnormalities are morphologically visible signs of altered brain development. There have been reported psychiatric associations between mega cisterna magna, including schizophrenia, and ASD. Children with low functioning autism may have a high rate of mild neuroradiologic abnormalities, which could further the study of different endophenotypes and complete the clinical evaluation of ASD children. ^[11]

Byrne et al., (2023) found that 7.2% of children whose only neuroimaging indication was ASD had abnormal brain MRI, which were more frequently associated with abnormal neurological examinations or genetic/metabolic abnormalities. ^[12]

This study showed that GARS-3 total raw score, GARS-3 social interaction score and GARS-3 communication score were significantly higher in autistic children with Mega cisterna magna (mean was 43.5±0.7, 17±0 and 16±0 respectively) than in other findings.

This was in agreement with Binic et al., (2023) who reported that Mega cisterna magna is usually an unintentional radiographic finding, but it can also be linked to specific mental disorders where patients have poor perfor-mance on certain cognitive tasks, such as verbal fluency and memory. The mega cisterna magna is the most prevalent minor abnormality. A minor abnormality such as this is proposed as a marker for brain dysgenesis. Lower perfor-mance on speech tests (verbal and semantic fluency) is often associated with cisterna magna enlargements in children with ASD, which interfere with their communication and intera-ction with the surroundings and caregivers. ^[13]

As regard stereotyping score, mean was significantly higher in autistic children with benign enlargement of the subarachnoid space in MRI (14.6±1.8) than in other cases.

These results were agreed with Shen et al., (2013) who concluded that infants who suffered from ASD had significantly wide extra-axial fluid by 6–9 months of age. Extra-axial fluid is characterized by an excessive CSF in the subarachnoid space, presence of excessive extra-axial fluid which does not resolve by the second year of life may be a characteristic of infants who develop autism. Furthermore, the longer extra-axial fluid remained elevated, the more severe the ASD symptoms. increased extra-axial fluid during early infancy was associated with both a diagnosis of ASD and increase symptoms severity. Increased extra-axial fluid found at 6 months and continued to be increased through 24 months could be a predictive marker specific to ASD. ^[14]

These results were in contrast with Peterson et al., (2021) who found that between 3 and 42 years, there were no group differences in extra-axial CSF volume. These findings imply that beyond the age of four, the elevated extra-axial CSF volume in early autistic children returns to normal. ^[15]