Research

Factors Associated with Symptom Persistence in PANS: Part II—Presenting Features, Medical Comorbidities, and IVIG Treatment History
Denise Calaprice-Whitty, Angela Tang, and Janice Tona.Factors Associated with Symptom Persistence in PANS: Part II—Presenting Features, Medical Comorbidities, and IVIG Treatment History.Journal of Child and Adolescent Psychopharmacology.Nov 2023.365-377.http://doi.org/10.1089/cap.2023.0023
  • Significant relationships were identified among the 646 subjects, linking greater symptom persistence to higher rates of medical comorbidities.
  • Specific comorbidities associated with greater symptom persistence included rashes, headaches, chronic sinusitis, frequent diarrhea, and immune deficiencies.
  • Developmental diagnoses and respondent-perceived developmental lags were more prevalent in subjects with greater symptom persistence.
  • Subjects with greater symptom persistence reported PANS exacerbations associated with infections in close contacts, vaccinations, environmental triggers, and exacerbations of comorbidities.
  • PANS recurrences were more likely to be triggered by Epstein Barr Virus, mycoplasma, and sinus infections in subjects with greater symptom persistence.
  • More persistent PANS was linked to significantly higher frequencies of certain symptoms, including sleep disturbance, urinary incontinence, muscle pain, brain fog, sensory defensiveness, irritability, and aggression-related symptoms.
  • The effectiveness of intravenous immunoglobulin in combating symptoms was found to be less in cases of more persistent PANS.
  • Subjects with greater symptom persistence experienced more difficulty attending school.

“Conclusions: Our results suggest high symptom persistence in PANS to be associated with more pervasive medical and neuropsychiatric symptoms. Differences in symptom persistence are associated with both intrinsic (e.g., immune competence) and extrinsic (e.g., infections, treatment) factors. Because extrinsic factors are potentially modifiable, it is critical that providers be aware of current guidelines on PANS evaluation and treatment.”

Factors Associated with Symptom Persistence in PANS: Part I—Access to Care
Calaprice-Whitty D, Tang A, Tona J. Factors Associated with Symptom Persistence in PANS: Part I-Access to Care. J Child Adolesc Psychopharmacol. 2023 Nov;33(9):356-364. doi: 10.1089/cap.2023.0022. Epub 2023 Oct 30. PMID: 37902790.
  • Greater symptom persistence correlated with longer intervals between symptom onset and treatment (F = 4.43, p = 0.002).
  • Subjects with the least symptom persistence (>75% symptom-free days) were diagnosed by the first practitioner seen in 34% of cases, compared to 13% in those with the most persistent symptoms (symptoms every day) (L-R χ2 = 36.55, p < 0.0001).
  • Lack of access to expertise did not impede diagnosis and treatment for 52% of subjects with the least persistent symptoms, contrasting with 22% in those with the most persistent symptoms (L-R χ2 = 22.47, p < 0.0001).
  • Affordability did not impact diagnosis and treatment for 76% of subjects with the least persistent symptoms, whereas it affected 42% of those with the most persistent symptoms (L-R χ2 = 27.83, p < 0.0001).
  • Subjects whose PANS symptoms resolved with antibiotic treatment had less symptom persistence than others (χ2 = 23.27, p = 0.0001).
  • More persistently symptomatic subjects were more likely to discontinue intravenous immunoglobulin (IVIG) treatment due to access-to-care reasons.

“Conclusions: Unimpeded access to care for PANS is associated with more symptom-free days over reporting periods averaging approximately 4 years. Difficulty reaching expert providers, missed opportunities for diagnoses, and financial limitations may worsen outcomes. Practitioners, particularly primary providers, should adhere to published diagnostic and treatment guidelines promptly upon presentation.”

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease
La Bella S, Scorrano G, Rinaldi M, Di Ludovico A, Mainieri F, Attanasi M, Spalice A, Chiarelli F, Breda L. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease. Microorganisms. 2023 Oct 13;11(10):2549. doi: 10.3390/microorganisms11102549. PMID: 37894207; PMCID: PMC10609001.
Despite significant advances in the understanding of the pathogenesis and therapeutic management of affected children, PANDAS remains a subject of dispute among experts. The controversial issues discussed in this paper can primarily be attributed to the challenges associated with establishing a definitive and timely correlation between the occurrence or recurrence of OCD and tic disorder in children who experience multiple GAS infections. Furthermore, it is important to note that the existing research examining the effectiveness of treatment techniques suffers from limitations in terms of sample size and rigorous inclusion criteria, which consequently hinders the provision of robust recommendations. Additional research is required to enhance our comprehension of the real prevalence of the disease, the precise pathogenic pathways involved, and the appropriate evidence-based methodology for its treatment.
Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome
Eremija J, Patel S, Rice S, Daines M. Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome. Front Pediatr. 2023 Oct 16;11:1229150. doi: 10.3389/fped.2023.1229150. PMID: 37908968; PMCID: PMC10613689.
  • A 5-year retrospective study was undertaken in Children’s Postinfectious Autoimmune Encephalopathy Center at University of Arizona.
  • 12 children diagnosed with PANS and treated with immunomodulatory IVIG dose who completed neuropsychological testing before and after treatment
  • Participants received 1–7 IVIG courses.
  • Improvement occurred in 11/12 patients, in one or multiple domains/subdomains, independently of time between disease onset and IVIG initiation (0–7 years)
  • Improvement was primarily seen in memory (58%), sensory-motor (37%) and visual-motor integration (30%).
  • 5/12 had hypogammaglobulinemia requiring ongoing IVIG replacement. Emphasizes the presumed role of immune dysfunction in disease pathogenesis.
  • 1/12 had isolated low IgA. 1/12 discontinued IVIG therapy due to severe adverse effects
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections Manifestations in a Teenager

Sivakanthan A, Gedeon J, Sadaf S, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections manifestations in a teenager. Prim Care Companion CNS Disord. 2023;25(5):23cr03505. October 5, 2023. https://doi.org/10.4088/PCC.23cr03505

This is a case of an 18-year-old male patient with PANDAS resistant to most treatments recommended in the literature. The patient lives with his parents, was recently home schooled, and has a history of autoimmune encephalitis, OCD, and Tourette’s disorder. He was admitted to an inpatient psychiatric unit for daily physical aggression toward his parents.

Estimate of the incidence of PANDAS and PANS in 3 primary care populations
Wald ER, Eickhoff J, Flood GE, Heinz MV, Liu D, Agrawal A, Morse RP, Raney VM, Veerapandiyan A, Madan JC. Estimate of the incidence of PANDAS and PANS in 3 primary care populations. Front Pediatr. 2023 Sep 21;11:1170379. doi: 10.3389/fped.2023.1170379. PMID: 37808558; PMCID: PMC10551157.

Results: The combined study population consisted of 95,498 individuals. The majority were non-Hispanic Caucasian (85%), 48% were female and the mean age was 7.1 (SD 3.1) years. Of 357 potential cases, there were 13 actual cases [mean age was 6.0 (SD 1.8) years, 46% female and 100% non-Hispanic Caucasian]. The estimated annual incidence of PANDAS/PANS was 1/11,765 for children between 3 and 12 years with some variation between different geographic areas.

Conclusion: Our results indicate that PANDAS/PANS is a rare disorder with substantial heterogeneity across geography and time. A prospective investigation of the same question is warranted.

Post-infectious inflammation, autoimmunity, and OCD: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Disorder (PANS)

A Vreeland; D Calaprice; N Or-Geva; RE. Frye; D Agalliu; HM. Lachman; C Pittenger; S Pallanti; K Williams; M Ma; M Thienemann; A Gagliano; E Mellins; J Frankovich https://doi.org/10.1159/000534261

In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease)in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.

Living with Paediatric acute-onset neuropsychiatric syndrome (PANS) – a qualitative study of Children’s experiences in Sweden

N Ringer, C Benjaminson, H Bejnö, Living with Paediatric acute-onset neuropsychiatric syndrome (PANS) – a qualitative study of Children’s experiences in Sweden. Cogent Psychology (2023), 10: 2259745 DOI:10.1080/23311908.2023.2259745

The study aimed to understand the experience of living with PANS from the perspective of children with the diagnosis.

  • PANS causes suffering due to the aversive emotional, cognitive, and physical experiences and the negative consequences the symptoms cause. The dramatic and abrupt onset plus the nature of the symptoms cause intense fear.
  • PANS makes them feel that they have no control or power over their lives. It is complicated due to the difficulty in predicting and managing symptoms. Also, difficult to describe their needs. It is difficult to work with providers who do not listen or really try to understand their needs and experiences.
  • Meaningful support consists of having someone who does not give up and will continue trying treatments. Also, caregivers who are stable, empowering, and supportive are important.
Clinicopathologic Characteristics of PANDAS in a Young Adult: A Case Report
Kulumani Mahadevan LS, Murphy M, Selenica M, Latimer E, Harris BT. Clinicopathologic Characteristics of PANDAS in a Young Adult: A Case Report. Dev Neurosci. 2023;45(6):335-341. doi: 10.1159/000534061. Epub 2023 Sep 12. PMID: 37699369; PMCID: PMC10753865.

Although this disease is primarily thought to be a disease of childhood, it is reported to occur also in adults. PANDAS is a well-defined clinical entity, but the neuropathology of this condition has not been established yet. We describe the clinical course of a 26-year-old female diagnosed with PANDAS. She committed suicide and her brain was biobanked for further studies. We examined the banked tissue and performed special stains, immunohistochemical, and immunofluorescence analyses to characterize the neuropathology of this condition. Histology of the temporal lobes, hippocampus, and basal ganglia shows mild gliosis and Alzheimer’s type II astrocytes. Acute hypoxic ischemic changes were noted in hippocampus CA1 and CA2 areas. Immunostaining shows increased parenchymal/perivascular GFAP staining and many vessels with mild increases in CD3-, CD4-, and CD25-stained lymphocytes in the basal ganglia. The findings suggest that CD4- and CD25-positive T cells might have an important role in understanding the neuroinflammation and pathogenesis of this condition. The case represents the first neuropathological evaluation report for PANDAS.

An Exploratory Study of Obsessive-Compulsive Behavior and School Problems Associated with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)
Maura A. Miglioretti, Ara J. Schmitt, Kara E. McGoey & M. Tina Benno (2023) An Exploratory Study of Obsessive-Compulsive Behavior and School Problems Associated with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), Journal of Applied School Psychology, DOI: 10.1080/15377903.2023.2263391
  • Parents (n = 208) of children with PANS participated in this study by completing a survey that included the Children’s Yale-Brown Obsessive-Compulsive Scale Parent Report (CY-BOCS-PR) and additional questions regarding child school performance and participation in formal special services at school.
  • Anxiety and inattention, among a variety of other school-based problems, are reported at school in this population.
  • Approximately 60% of the children received some form of school special services across their educational career.
  • A variety of mild to severe obsessive-compulsive behaviors were reported in the children, though the severity of those behaviors did not predict the existence of a school special services plan.
  • School psychologists must be prepared to evaluate children with PANS and recommend evidence-based interventions.
Symptom flares after COVID-19 infection versus vaccination among youth with PANS/PANDAS
LaRusso MD, Abadia CE. Symptom flares after COVID-19 infection versus vaccination among youth with PANS/PANDAS. Allergy Asthma Proc. 2023 Sep 1;44(5):361-367. doi: 10.2500/aap.2023.44.230049. PMID: 37641227; PMCID: PMC10476495.

These results support COVID-19 vaccination for most individuals with PANS/PANDAS given that the frequencies of symptom flares and setbacks after COVID-19 infection were significantly higher than after the COVID-19 vaccine. Nonetheless, further studies are needed to fully assess the risk-benefit balance and to provide a more individualized approach to disease prevention in people with immune vulnerabilities.

The PANDAS/PANS disorders. Is it time for more allergist-immunologists to get involved?
Bellanti JA. The PANDAS/PANS disorders. Is it time for more allergist-immunologists to get involved? Allergy Asthma Proc. 2023 Sep 1;44(5):296-305. doi: 10.2500/aap.2023.44.230029. PMID: 37641225.
Conclusion: The PANDAS/PANS disorders are a continuing burden for growing numbers of patients, health-care providers, and the global health-care systems, and are a particular challenge for the allergist/immunologist who is increasingly being called upon for their management. Because of the importance of immunologic factors in the pathogenesis and treatment of these conditions with anti-inflammatory and immune-modulating treatments, the allergist/immunologist is well poised to offer consultative care.