The COVID-19 pandemic and children with PANS/PANDAS: an evaluation of symptom severity, telehealth, and vaccination hesitancy

O’Dor, S.L., Zagaroli, J., Belisle, R. et al. The COVID-19 pandemic and children with PANS/PANDAS: an evaluation of symptom severity, telehealth, and vaccination hesitancy. Child Psychiatry Hum Dev (2022). https://doi.org/10.1007/s10578-022-01401-z

  • Assessed the impact of the COVID-19 pandemic on children with PANS/PANDAS
  • A majority of respondents endorsed a negative impact on their child’s friendships, relationships with extended family, hobbies, and academic skills due to the pandemic
  • Children with suspected or diagnosed COVID-19 experienced new or worsened psychiatric symptoms, particularly mood lability, OCD, and anxiety
  • Telehealth care was the preferred treatment modality if the child had mild symptoms of PANS/PANDAS
  • Caregivers experienced a high level of burn-out both before and during the pandemic, and thus this should continue to be an area of inquiry and appropriate intervention by providers
  • Data suggest an overall negative impact of the COVID-19 pandemic on children with PANS/PANDAS and their caregivers.
Further Understanding of Neuro-Immune Interactions in Allergy: Implications in Pathophysiology and Role in Disease Progression

Konstantinou GN, Konstantinou GN, Koulias C, Petalas K, Makris M. Further Understanding of Neuro-Immune Interactions in Allergy: Implications in Pathophysiology and Role in Disease Progression. J Asthma Allergy. 2022;15:1273-1291. https://doi.org/10.2147/JAA.S282039

“We have systematically reviewed and discussed the evidence regarding the role of the neuro-immune interactions in common allergic clinical modalities like allergic rhinitis, chronic rhinosinusitis, allergic asthma, food allergy, atopic dermatitis, and urticaria. It is essential to understand unknown – to most of the immunology and allergy experts – neurological networks that not only physiologically cooperate with the immune system to regulate homeostasis but also pathogenetically interact with more or less known immunological pathways, contribute to what is known as neuroimmunological inflammation, and shift homeostasis to instability and disease clinical expression.”

Psychobiotics: the Influence of Gut Microbiota on the Gut-Brain Axis in Neurological Disorders

Oroojzadeh, P., Bostanabad, S.Y. & Lotfi, H. Psychobiotics: the Influence of Gut Microbiota on the Gut-Brain Axis in Neurological Disorders. J Mol Neurosci (2022). https://doi.org/10.1007/s12031-022-02053-3

  • Psychobiotics are a probiotic strain capable to affect the gut-brain axis.
  • Finding suggests that Psychobiotics can efficiently alleviate the symptoms of several CNS disorders such as autism spectrum disorders, Parkinson’s disease, multiple sclerosis, insomnia, depression, diabetic neuropathy, and anorexia nervosa.
  • It can be concluded that functional foods containing psychotropic strains can help to improve mental health.
Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients

T Bhikram, P Sandor, Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients, Brain, Behavior, and Immunity, Volume 105, 2022, Pages 237-246, https://doi.org/10.1016/j.bbi.2022.07.006.

Conclusion: The consistent findings of elevated NLR across the reviewed psychiatric disorders suggest that abnormal NLR is not specific to any one disorder but may reflect a pathological brain process that leads to brain dysfunction. These findings support hypotheses of neuroinflammation being important to the etiology of psychiatric disorders. More research is needed to further elucidate the relationship between specific diagnostic and behavioural constructs and NLR. Future work is also needed to determine the specific neuroinflammatory mechanisms that give rise to specific disorders.

A Case of Steroid-Responsive Severe Pneumonia Following a Recent COVID-19 Infection in a Patient With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection

Pourshahid S, Khademolhosseini S, Giri B, et al. (July 12, 2022) A Case of Steroid-Responsive Severe Pneumonia Following a Recent COVID-19 Infection in a Patient With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection. Cureus 14(7): e26785. doi:10.7759/cureus.26785

“Drug-induced pneumonitis was a possibility as well; however, she was only taking rituximab and cetirizine. Rituximab is a potential agent for the treatment of pneumonitis refractory to conventional treatments [25]. Although there are a few reported cases of rituximab-induced pneumonitis [26], the three-month delay after the last injection of rituximab and rapid progression in a few days are not consistent with drug-induced pneumonitis.

It is conceivable that her recent COVID-19 infection may have activated an exaggerated inflammatory response as the immunosuppression related to rituximab was subsiding. The rapidly progressing pulmonary consolidations and worsening respiratory symptoms under these circumstances should prompt the clinician to consider steroid-responsive-pneumonia like post-COVID OP, MISA, and IRIS-like reactions. Rapid institution of high-dose steroids seems to be the key to treatment. Whether her history of PANDAS may have further impacted her immune system, making her more prone to this exaggerated response is unclear.”

Identification of ultra‑rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing

Trifiletti R, Lachman HM, Manusama O, Zheng D, Spalice A, Chiurazzi P, Schornagel A, Serban AM, van Wijck R, Cunningham JL, Swagemakers S, van der Spek PJ. Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing. Sci Rep. 2022 Jun 30;12(1):11106. doi: 10.1038/s41598-022-15279-3. PMID: 35773312. – Open Access

  • The pathological mechanisms are likely heterogeneous, but we hypothesize convergence on one or more biological pathways.
  • Conducted whole exome sequencing (WES) on a U.S. cohort of 386 cases, and whole genome sequencing (WGS) on ten cases from the European Union who were selected because of severe PANS.
  • Focused on identifying potentially deleterious genetic variants that were de novo or ultra‑rare (MAF) < 0.001. Candidate mutations were found in 11 genes (PPM1D, SGCE, PLCG2, NLRC4, CACNA1B, SHANK3, CHK2, GRIN2A, RAG1, GABRG2, and SYNGAP1) in 21 cases, which included two or more unrelated subjects with ultra‑rare variants in four genes.
  • These genes converge into two broad functional categories.
    • One regulates peripheral immune responses and microglia (PPM1D, CHK2, NLRC4, RAG1, PLCG2).
    • The other is expressed primarily at neuronal synapses (SHANK3, SYNGAP1, GRIN2A, GABRG2, CACNA1B, SGCE). Mutations in these neuronal genes are also described in autism spectrum disorder and myoclonus‑dystonia.
  • 12/21 cases developed PANS superimposed on a preexisting neurodevelopmental disorder. Genes in both categories are also highly expressed in the enteric nervous system and the choroid plexus.
  • Thus, genetic variation in PANS candidate genes may function by disrupting peripheral and central immune functions, neurotransmission, and/or the blood‑CSF/brain barriers following stressors such as infection

 

Adverse Childhood Events, Post-Traumatic Stress Disorder, Infectious Encephalopathies and Immune-Mediated Disease

Citation: Bransfield, R.C. Adverse Childhood Events, Post-Traumatic Stress Disorder, Infectious Encephalopathies and Immune-Mediated Disease. Healthcare 2022, 10, 1127. https://doi.org/10.3390/healthcare10061127

“In summary, insight into the underlying pathophysiology of Adverse Childhood Events, Post-Traumatic Stress Disorder, and infectious encephalopathies offers expanded treatment opportunities that include psychotherapeutic treatments that help to differentiate safety vs. danger, therapies to improve empowerment, and psychotropic medications to reduce intrusive symptoms and other symptoms, anti-infective treatments, immune-modulating treatments and education for patients and caregivers.“

Paediatric autoimmune neuropsychiatric syndrome in recurrent acute bacterial pharyngitis – a case report

Paediatric autoimmune neuropsychiatric syndrome in recurrent acute bacterial pharyngitis – a case report.  Pepaś, Renata; Przysło, Łukasz; Konopka, Wiesław. Paediatrics and Family Medicine; Warsaw Vol. 18, Iss. 1,  (2022): 84–88. DOI:10.15557/PiMR.2022.0011

Abstract: Pharyngitis and tonsillitis, regardless of their aetiology, are one of the most frequent reasons for visiting a family doctor or a paediatrician. Nearly 85% of pharyngitis cases are viral. It is estimated that bacterial throat infection occurs in 15% of school- age children and in 4–10% of adult patients. Streptococcus pyogenes is the most common cause of bacterial pharyngitis.
PANDAS stands for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. The term is used to describe a subgroup of children and adolescents who develop acute obsessive-compulsive disorder or tics as a result of group A streptococcal infection, such as tonsillitis. The aim of the paper is to describe a case of a 4-year-old boy who presented to the Laryngology Clinic due to recurrent tonsillitis, time-correlated with obsessive-compulsive disorder.

Untimely care: How the modern logics of coverage and medicine compromise children’s health and development

M LaRusso, DF Gallego-Pérez, CE Abadía-Barrero. Untimely care: How the modern logics of coverage and medicine compromise children’s health and development, Social Science & Medicine, 2022, 114962, DOI: 10.1016/j.socscimed.2022.114962.

  • Coverage problems for controversial conditions exist across health care systems.
  • Modern medicine fails to support new and controversial conditions like PANS/PANDAS.
  • Despite being insured, many children face barriers to diagnosis and treatment.
  • The modern logics of medicine and coverage fail to provide care in PANS/PANDAS.
  • Failures to care result in developmental disruptions in children with PANS/PANDAS.
Children With PANS May Manifest POTS

Chan A, Gao J, Houston M, Willett T, Farhadian B, Silverman M, Tran P, Jaradeh S, Thienemann M, Frankovich J. Children With PANS May Manifest POTS. Frontiers in Neurology. Vol 13, 2022 DOI: 10.3389/fneur.2022.819636

  • 204 patients: mean age of PANS onset was 8.6 years, male sex (60%), non-Hispanic White (78%).
  • Evidence of POTS was observed in 19/204 patients (9%). 5/19 have persistent POTS
  • Those with PANS & POTS were more likely to have
    • comorbid joint hypermobility (63 vs 37%, p = 0.04)
    • chronic fatigue (42 vs 18%, p = 0.03)
    • family history of chronic fatigue, POTS, palpitations and syncope
  • Showed a PANS flare was significantly associated with an exacerbation of POTS symptoms (OR 3.3, 95% CI 1.4–7.6, p < 0.01)
Unexplained post-acute infection syndromes

Choutka, J., Jansari, V., Hornig, M. et al. Unexplained post-acute infection syndromes. Nat Med 28, 911–923 (2022). https://doi.org/10.1038/s41591-022-01810-6

“SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine. The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis. In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.”

Understanding parental stress among parents of children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) in Sweden
Noam Ringer & Lise Roll-Pettersson (2022) Understanding parental stress among parents of children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) in Sweden, International Journal of Qualitative Studies on Health and Well-being, 17:1, DOI:10.1080/17482631.2022.2080906
The study illuminates how parents’ perceptions of the child’s symptoms, parents’ strategies for managing problems, as well as experiences related to healthcare providers, may increase or decrease parental stress.
  • The analysis of interviews resulted in five identified categories, which together reflect aspects related to parental stress in parents of a child with PANS.
  • The first three categories reflect parents’ appraisals related to the condition:
    • “Being effected by PANS”
    • “Experiencing PANS over and over again
    • “Having no control”
  • The fourth category, “Obtaining medical treatment is challenging”, entails appraisals related to contact with clinicians
  • The fifth category, “Managing problems”, consists of strategies parents apply in order to manage problems related to having a child with PANS

 

Leah’s Story

Leah’s Story

In August of 2014 our daughter, Leah, was 6 years old.  We had just returned home from a month-long trip to Illinois to visit family.  When we arrived home in Arizona, she suddenly (overnight) developed a fear of vomit.