Speaker
Description
Chiari Malformation Type I (CM1), characterized by cerebellar tonsillar herniation exceeding 5 mm through the foramen magnum, represents the most common subtype of Chiari Malformations, a group of developmental disorders involving posterior fossa deformities. Despite its prevalence characterized by a strong female predominance, its described neuroanatomical features, neurological symptoms, and neurosurgical treatments, CM1’s is often underdiagnosed because of interpersonal and sociodemographic factors, leading to disparities in treatment access. Additionally, classical manifestations of CM1 are often accompanied by the occurrence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), which are currently poorly considered as well as the genetic and molecular underpinnings which remain largely unknown.
This systematic review integrates findings from 50 original research articles, sourced from PubMed and Medline databases, and explores CM1 through neuropsychological, neuropsychiatric, genetic, and genomic research methodologies. We aim to bridge traditionally siloed research domains, proposing a discipline-overarching understandings of CM1, highlighting the cerebellum’s non-motor functions by deconstructing the genetic, familial and environmental factors through “CM1 Equifinality” in the occurrence of this disorder, investigating its frequent presence in both neurodevelopmental and psychiatric conditions, syndromes and its presentation along cognitive impairment and emotion dysregulation. Thereby, we address key research gaps including CM1’s multifactorial pathogenesis and population-level outcomes.
With this work we want to emphasize the critical need for psychiatric monitoring, neuropsychological interventions, and psychotraumatological implications in high-risk pediatric populations for CM1 within the general population. We want also to highlight how CM1 represents a unique model of study integrating developmental biology, cognition, and psychiatry through a cerebellar lens. Lastly, in light of the recent advances in patient-derived models foreseeing the use of 3D in vitro models to recapitulate cellular and molecular features of ASD and ADHD (both CM1 comorbidities), we propose cerebellar organoids as potential tool to investigate the neurogenomic bases of this disease.
| Author(s) | Irmak Oezdil*12, Davide Aprile3, Giuseppe Testa345, Christian Beste167 |
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| Affiliation(s) | "1Faculty of Psychology, School of Science, TU Dresden, Dresden, Germany 2 Department of Psychotherapy and Psychosomatic Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany 3Human Technopole, Viale Rita Levi Montalcini 1, 20157 Milan, Italy. 4 Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, Italy. 5 Department of Experimental Oncology, IEO, European Institute of Oncology, IRCCS, 20139 Milan, Italy. 6 Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany 7 University Neuropsychology Center, Faculty of Medicine, TU Dresden, Dresden, Germany." |
