Paediatric Acute Onset Neuropsychiatric Syndrome with Alternative Factors Perspective
M3 India Newsdesk Jan 22, 2025
This article explores alternative factors contributing to unresolved Paediatric Acute Onset Neuropsychiatric Syndrome PANS beyond infections, including autoimmune mechanisms, environmental triggers, metabolic disorders, and genetic predispositions.
Paediatric Acute Onset Neuropsychiatric Syndrome PANS
Paediatric Acute Onset Neuropsychiatric Syndrome (PANS) is characterised by the sudden onset of obsessive-compulsive symptoms and/or severe anxiety, often preceded by an infection. While streptococcal infections remain the most frequently cited trigger, many cases remain unresolved despite appropriate treatment.
Paediatric Acute Onset Neuropsychiatric Syndrome (PANS) presents a challenging clinical picture primarily characterised by the abrupt onset of obsessive-compulsive disorder (OCD), anxiety, and other behavioural changes in children.
The critical aspect of PANS is its sudden onset, often linked to infections, particularly Group A Streptococcus (GAS) [1]. However, a significant subset of cases poses challenges for management, as they do not respond to conventional treatments. Therefore, it is crucial to identify and understand alternative factors contributing to unresolved PANS.
Autoimmune mechanisms
- Emerging evidence suggests that autoimmune responses may play a crucial role in the pathogenesis of PANS.
- Autoantibodies have been identified in some patients with PANS, raising the possibility of an autoimmune basis for the syndrome [2].
- For instance, antibodies targeting the dopamine receptor D1 have been implicated in neuropsychiatric symptoms [3].
- Additionally, the concept of post-infectious autoimmune encephalitis underlines that not all neuropsychiatric disorders triggered by infections are directly related to the infectious agent but rather to subsequent autoimmune responses [4].
Molecular mimicry and cross-reactivity
Molecular mimicry, whereby the immune system mistakenly targets host tissue that shares structural similarities with pathogen components, has been suggested as a mechanism in unresolved cases.
Recurrent infections could lead to persistent inflammatory responses that adversely affect the nervous system, resulting in ongoing neuropsychiatric symptoms [5].
Environmental triggers
- Environmental factors, including exposure to toxins, play a significant role in neuropsychiatric disorders.
- For example, recent studies link heavy metal exposure, such as lead and mercury, to cognitive and behavioural issues in children [6].
- In the context of PANS, environmental stressors may aggravate pre-existing vulnerabilities or contribute to psychopathology by influencing inflammatory pathways or neurodevelopment [7].
Psychosocial stressors
Psychosocial stressors also warrant consideration. Children facing significant life transitions or stress (e.g., divorce, bullying, or trauma) could exhibit exacerbated symptoms that mimic PANS [8]. A comprehensive approach to treatment must evaluate these psychosocial contexts to address potential underlying contributors.
Metabolic disorders
Metabolic disorders can lead to symptoms that mimic PANS, complicating diagnosis and treatment. Conditions like mitochondrial dysfunction and abnormalities in neurotransmitter metabolism have been documented to affect behavioural and cognitive functioning [9]. Clinicians should consider metabolic evaluations in cases of unresolved PANS to rule out or adequately manage these underlying conditions.
Genetic predispositions
Genetic factors might also play a significant role in vulnerability to PANS. Familial patterns of neuropsychiatric disorders have been observed, suggesting heritable components [10]. Specific genetic polymorphisms involved in immune responses and neurotransmitter systems may predispose children to PANS or influence the severity and persistence of symptoms [11].
Unresolved Paediatric Acute Onset Neuropsychiatric Syndrome represents a clinical conundrum that warrants a multifaceted approach to diagnosis and treatment. Beyond infectious triggers, numerous alternative factors, including autoimmune mechanisms, environmental influences, metabolic disorders, and genetic predispositions, contribute to the complexity of this syndrome. A comprehensive assessment of these factors is essential for successful management, emphasising the need for interdisciplinary collaboration among clinicians, researchers, and families.
Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.
About the author of this article: Dr Partha Ghosh, BNYS, MD(YS), is a general physician and a medical writer from Siliguri, Darjeeling.
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