Neural Regen Res. 2026 Jan 27. doi: 10.4103/NRR.NRR-D-25-00734. Online ahead of print.

ABSTRACT

With the advancing understanding of autism spectrum disorder comorbid with epilepsy, a growing body of research has recently focused on the specific comorbidity of autism spectrum disorder and epilepsy. This paper reviews the current state of research and prospects regarding the etiology, mechanisms, and treatment of autism spectrum disorder comorbid with epilepsy. Current research on the causes of this comorbidity suggests that a combination of hereditary and environmental factors plays a role. Genetic causes include gene mutations, chromosomal copy number variations, and single nucleotide polymorphisms. Environmentally, factors such as imbalanced nutrient intake and prenatal exposure to sodium valproate are notably associated with this comorbidity. The imbalance between excitation and inhibition emerges as the most critical pathophysiological process, primarily involving the GABAergic and glutamatergic systems. Additionally, dysfunction in glial cells, particularly astrocytes, exacerbates this imbalance. As a result, the brain fails to establish normal networks during development, leading to clinical manifestations such as social dysfunction, repetitive and stereotypic behaviors, and epileptic seizures. Conversely, immunological mechanisms, such as maternal immune activation, are key factors in the comorbidity of autism spectrum disorder and epilepsy, influenced by environmental factors, and provide insights for prevention. Current treatments include pharmacotherapy, neurostimulation, dietary therapy, and immunotherapy. Pharmacotherapy mainly manages symptoms, with drugs such as cannabidiol showing promise but lacking robust clinical evidence. Neurostimulation, a promising treatment, is divided into invasive and non-invasive methods. Invasive techniques, such as deep brain stimulation and vagus nerve stimulation, are used for drug-resistant epilepsy and can also improve the symptoms of autism spectrum disorder. Non-invasive neurostimulation methods, such as transcranial electrical and magnetic stimulation, are still in the early research stages and require further validation. Dietary therapy offers potential for managing comorbidities through food selectivity interventions, nutrient supplements, and specialized diets. Immunotherapy is proposed based on the immunological aspects of these comorbidities, but further study is needed. This review helps enhance the understanding of treatment mechanisms by examining the causes and development of autism spectrum disorder and epilepsy. It recommends a clinical approach based on the “etiology-mechanism-treatment” model.

PMID:41622472 | DOI:10.4103/NRR.NRR-D-25-00734

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