Research

A Paradigm Shift in the Utilization of Therapeutic Plasmapheresis in Clinical Practice

Kiprov DD, A Paradigm Shift in the Utilization of Therapeutic Plasmapheresis in Clinical Practice.
Ann Clin Med Case Rep. 2023; V12(5): 1-7. ISSN 2639-8109 Volume 12

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We report our experience in treating patients with TPE on an outpatient basis with several different medical conditions (Alzheimer’s disease, Long Covid, PANDAS) and prophylactically in older individuals for the attenuation of inflammaging.

PANDAS is another condition that is the result of postinfectious autoimmunity mediated through cross-reactive antibodies produced against molecular “mimics” or epitopes on the GAS cells that resemble host antigens [24]. Removal of these autoantibodies with TPE should result in symptomatic improvement.

We treated 7 patients with PANDAS over a period of 2 years. Patients were referred for TPE because they had severe symptoms with marked impairment of function at home, at school
and with peers, and had not responded to treatment with antibiotics, corticosteroids, and high dose IVIG.

 

 

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Syndrome: A 10-Year Retrospective Cohort Study in an Italian Centre of Pediatric Rheumatology

La Bella S, Attanasi M, Di Ludovico A, Scorrano G, Mainieri F, Ciarelli F, Lauriola F, Silvestrini L, Girlando V, Chiarelli F, et al. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Syndrome: A 10-Year Retrospective Cohort Study in an Italian Centre of Pediatric Rheumatology. Microorganisms. 2024; 12(1):8. https://doi.org/10.3390/microorganisms12010008

PANDAS syndrome, a rare condition in prepubertal children, presents with sudden tic disorders and/or OCD following a documented GAS infection. Current classification criteria lack specificity, resulting in misdiagnosis. In our study, 61 patients were screened by the Pediatric Rheumatology unit for suspected PANDAS, but only 19 met the criteria. Tic disorders, especially in the eyes and head/neck, were predominant, with common vocal tics and less documented OCD. Treatment with antibiotics often led to clinical improvement. Larger, controlled studies are essential to understanding PANDAS characteristics and therapeutic responses comprehensively.

The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox

Rao, A.P., Patro, D. The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox. Indian J Pediatr (2023). https://doi.org/10.1007/s12098-023-04928-8

Besides genetic susceptibility, infections due to viruses, bacteria and protozoa have been implicated in the development of autoimmune diseases (AD). AD can be triggered in a genetically susceptible individual by infections that disrupt immunological tolerance towards self-antigens. Pathogens can initiate autoimmunity by way of molecular mimicry, bystander activation, epitope spreading or persistent infection with polyclonal activation. This review covers two main topics: (i) the mechanisms by which an infectious agent can trigger or worsen autoimmunity; and (ii) the correlation between specific infectious agents and AD in humans with special emphasis on multisystem inflammatory syndrome in children (MIS-C).

Concurrent Infection of the Human Brain with Multiple Borrelia Species
Golovchenko M, Opelka J, Vancova M, Sehadova H, Kralikova V, Dobias M, Raska M, Krupka M, Sloupenska K, Rudenko N. Concurrent Infection of the Human Brain with Multiple Borrelia Species. Int J Mol Sci. 2023 Nov 29;24(23):16906. doi: 10.3390/ijms242316906. PMID: 38069228; PMCID: PMC10707132.
  • Lyme disease (LD) spirochetes invade tissues, including the brain.
  • Immune evasion tactics: immune suppression, tolerance, antigenic variation, intracellular hiding, biofilms, and persistent forms.
  • Immune-privileged site invasion (e.g., brain) shields spirochetes from immune response and antibiotics.
  • Case study: Spirochetal DNA found in multiple brain regions of a deceased LD patient.
  • Co-infection detected: Borrelia burgdorferi and Borrelia garinii in distinct, non-overlapping brain areas.
  • Atypical spirochete morphology observed in both human and experimentally infected mouse brain tissue.
Caregiver Burden, Stress, and Relationship Cohesion Among Self-Identified Caregivers of Children with PANS
Tona JT, Ash J, Brown E, Campagna C, Kostek K, Lawton E, Rieth A, Tomita M. Caregiver Burden, Stress, and Relationship Cohesion Among Self-Identified Caregivers of Children with Pediatric Acute-Onset Neuropsychiatric Syndrome. J Child Adolesc Psychopharmacol. 2023 Nov;33(9):378-386. doi: 10.1089/cap.2023.0030. PMID: 37966363; PMCID: PMC10771873.
  • Among the 216 respondents, 79.6% exceeded the CBI threshold, indicating a need for respite in adult care receiver populations. On the CSAQ, 72.9% expressed high distress, 80.5% reported feeling overwhelmed, and 58.1% reported crying spells, meeting cutoffs for support/respite used in adult care receiver populations.
  • The majority of caregivers (85.5%) reported not having the desired degree of cohesion with their child on the IOS. Parents of children with more severe PNSS symptoms performed significantly worse on all measures (CBI: H = 57.83; CSAQ: F = 29.26; IOS: H = 38.04; p < 0.001 for all).

Common Comment Themes

  1. Severe caregiver and/or family emotional distress and trauma.
  2. Caregivers wondering what happened to their child.
  3. Lack of awareness and support among health and education professionals.
  4. Relationship strain with family, friends, and significant others.
  5. Financial and/or legal struggles due to their child’s diagnosis.

“Conclusion: There is strong need for support and respite for children with PANS and their families. Long-term effects including posttraumatic stress symptoms among family members should be studied.”

Transcranial magnetic stimulation for developmental neuropsychiatric disorders with inflammation

Vaishnavi S. Transcranial magnetic stimulation for developmental neuropsychiatric disorders with inflammation. Developmental Neuroscience. 2023;45(6):342–348. doi:10.1159/000535103

  • Reviews transcranial magnetic stimulation (TMS) as a noninvasive technique that induces electrical changes in the brain via magnetic fields.Describes how repetitive TMS can modulate synaptic and network-level plasticity.

  • Notes that inflammation negatively affects synaptic plasticity and that TMS may help address inflammation-related dysfunction.

  • Summarizes evidence suggesting TMS may directly downregulate inflammatory processes.

  • Highlights potential utility of TMS for neuropsychiatric symptoms in inflammatory neurodevelopmental disorders, including autism, Tourette syndrome, and OCD.

  • Emphasizes that TMS is best viewed as a technology platform for modulating dysfunctional brain networks and may expand as understanding of network dysfunction grows

An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know
Hardin H, Shao W, Bernstein JA. An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know. Ann Allergy Asthma Immunol. 2023 Nov;131(5):567-575. doi: 10.1016/j.anai.2023.08.022. Epub 2023 Aug 25. PMID: 37634580.

Conclusion: Owing to the complexity and variability in ways patients with IAE may present to the allergist/immunologist office, an interdisciplinary approach is imperative to provide patients with the best medical care. Still, more research is needed to further elucidate the mechanism(s) and optimal treatment algorithm for IAE to facilitate broader recognition and acceptance of this condition by the medical community.

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