Research

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

Vitamin D deficiency and C-reactive protein: a bidirectional Mendelian randomization study

Ang Zhou, Elina Hyppönen, Vitamin D deficiency and C-reactive protein: a bidirectional Mendelian randomization study, International Journal of Epidemiology, 2022;, dyac087, https://doi.org/10.1093/ije/dyac087

Conclusion: The observed association between 25(OH)D and CRP is likely to be caused by vitamin D deficiency. Correction of low vitamin D status may reduce chronic inflammation.

Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models

Hoffman KL, Cano-Ramírez H. Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models. Expert Opin Drug Discov. 2022 May 11. doi: 10.1080/17460441.2022.2074396. Epub ahead of print. PMID: 35543072.

“Although data from existing animal models are consistent with an important role for anti-neuronal antibodies in PANS triggered by GAS infection, we lack models for identifying pathophysiological mechanisms of PANS associated with other infectious and non-infectious triggers. The authors propose a strategy for developing such models that incorporates known vulnerability and triggering factors for PANS into the modeling process. This novel strategy should expand our understanding of the pathophysiology of PANS, as well as facilitate the development of new pharmacological treatments for PANS and related syndromes.”

Bowel and Bladder Dysfunction Is Associated with Psychiatric Comorbidities and Functional Impairment in Pediatric Obsessive-Compulsive Disorder

Clara Westwell-Roper, John R. Best, Zainab Naqqash, Kourosh Afshar, Andrew E. MacNeily, and S. Evelyn Stewart.Journal of Child and Adolescent Psychopharmacology. Published Online: 11 Apr 2022 – ahead of printhttp://doi.org/10.1089/cap.2021.0059

“Neuropsychiatric disorders are common in children with bowel and bladder dysfunction (BBD), a syndrome associated with urinary frequency, urgency, holding, incontinence, and constipation. We evaluated BBD symptom severity in children and youth attending a tertiary care obsessive-compulsive disorder (OCD) clinic….. BBD symptoms are common and associated with high OCD-related impairment and psychiatric comorbidities. Standardized assessment may facilitate identification of BBD symptoms in this population and is critical to mitigating long-term physical and mental health impacts. Further studies are required to assess the relationship between BBD and OCD treatment outcomes.”

Reader Response: Lack of Association of Group A Streptococcal Infections and Onset of Tics

“Schrag et al. reported that Group A streptococcal (GAS) exposure is unrelated to tics in children at risk for tic disorders.¹ The critical limitations of this study are that only children with genetic risks for tics were studied and information about risk for autoimmunity, infection susceptibility, and antibiotics use are absent.¹ The EMTICS home page states that many patients refused to participate when told that antibiotic use would be limited. This would introduce a negative selection bias against families who perceive themselves as high risk and patients procuring antibiotics outside the trial.²“

In response to:

Schrag AE, Martino D, Wang H, Ambler G, Benaroya-Milstein N, Buttiglione M, Cardona F, Creti R, Efstratiou A, Hedderly T, Heyman I, Huyser C, Mir P, Morer A, Moll N, Müller NE, Müller-Vahl KR, Plessen KJ, Porcelli C, Rizzo R, Roessner V, Schwarz M, Tarnok Z, Walitza S, Dietrich A, Hoekstra PJ; European Multicentre Tics in Children Study (EMTICS). Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study. Neurology. 2022 Mar 15;98(11):e1175-e1183. doi: 10.1212/WNL.0000000000013298. Epub 2022 Feb 2. PMID: 35110379.