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IVIG

Hajjari, P., Oldmark, M.H., Fernell, E. et al. Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children. BMC Psychiatry 22, 535 (2022). https://doi.org/10.1186/s12888-022-04181-x

Conclusion: Considerable and pervasive improvements in symptoms and clinical impairments were seen in these ten children after three monthly IVIG treatments. Moderate to severe transient side effects occurred in three cases.

• Considerable improvements of PANS global symptoms and impairment were seen on the PANS Scale, CGI-S, CGI-I, and improved OCD symptoms on the CY-BOCS scale, lasting at least one month after the third IVIG treatment (at Visit 3).
• All children had improved at Visit 1 (one month after the first IVIG treatment).
• At Visit 3 – 8 of 10 children had lasting improvements, but 2 showed symptom rebounds
  • 1 patient had good but transient responses lasting only 2–3 weeks after each IVIG, followed by deteriorations
  • One had a concurrent viral infection at Visit 3.
• At baseline the severe symptoms had considerable impact on the children’s school attendance
  • Marked improvements in attendance were seen post-treatment
  • School absence during 3 months before baseline was 47% of the school days/month, compared to 13% after the third IVIG treatment.
• The main side effects were of a previously well-known type, i.e. transient headache, neck pain, nausea/vomiting (mild to severe), stomach pain, mild transient anemia, and brief allergic reaction.

DIAGNOSTICS, DIFFERENTIAL DIAGNOSTICS AND TREATMENT OF PANDAS SYNDROME: DESCRIPTION OF THE CASE. Mukhtorjonova Khusnigul Nodirbekovna, Elmurodova Zarina Aslanovna. Matkarimova Dilnoza Doniyorovna, Tashkent Pediatric Medical Institute. ISSN: 2776-0960 Volume 2, Issue 6, June 2021

The analysis of this clinical case demonstrates the existence of a group of patients with a good therapeutic response to the administration of immunoglobulins and antibiotics. The mechanisms of development and course of this condition are not fully understood and require further research.

Benefits of IVIG in Pediatric Acute-Onset Neuropsychiatric Syndrome

Isaac Melamed, Roger Kobayashi, Maeve O’Connor, Ai Lan Kobayashi, Andrew Schechterman, Melinda Heffron, Sharon Canterberry, Holly Miranda, Nazia Rashid Neurology Apr 14 2020, 94

“Conclusions: In PANS, which may be associated with an underlying immune dysregulation, IVIG [Octagam 5%] successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least 8 weeks, and up to 46 weeks, following the final infusion. In addition, baseline immune and autoimmune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterization, and study to clarify the potential immune dysfunction by which PANS manifests and progresses.”

Kathleen Connery, Marie Tippett, Leanna M. Delhey, Shannon Rose, John C. Slattery, Stephen G. Kahler, Juergen Hahn, Uwe Kruger, Madeleine W. Cunningham, Craig Shimasaki, Richard E. Frye
Transl Psychiatry-2018

In an open-labeled IVIG study in children with comorbid ASD and PANS/ PANDAS, anti-tubulin and anti-D2R (as measured by the Cunningham panel) were associated with responsiveness to IVIG treatment, suggesting that these autoantibodies could be biomarkers to select for positive IVIG treatment outcomes. Research continues to explore serum biomarkers and genetic risk factors that can provide a diagnostic tool and/or complement diagnosis in children with PANS/PANDAS.

Piero Pavone, Raffaele Falsaperia, Francesco Nicita, Andreana Zecchini, Chiari Battaglia, Alberto Spalice, Lucia Iozzi, Enrico Parano, Giovanna Vitaliti, Alberto Verrotti, Vincenzo Belcastro, Sung Yoon Cho, Dong-Kyu Jin, Salvatore Savasta 
Neuropsychiatry-2018
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In this cohort, 29 out of 34 of children treated with IVIG showed a reduction or disappearance of the symptomatology, while in 5 cases (15%), despite 3 IVIG courses, there was only temporary improvement of clinical symptoms, with their reappearance within 1 to 6 months. According to the results of literature and ours no definitive conclusions may be drawn from IVIG treatment for PANDAS. Limitations of the present study include the absence of casecontrols and long-term follow up. However, in our opinion, treatment with IVIG has been shown to be effective in PANDAS children with a serious-severe type and to be well tolerated. As it has been reported by Frankovic et al.  most of the PANS Research Consortium (PRC) members prefer use of IVIG in treatment of patients with this disorder in moderate to severe forms.

Kyle A. Williams, MD, PhD, Susan E. Swedo, MD, Cristan A. Farmer, PhD, Heidi Grantz, LCSW, Paul J. Grant, MD, Precilla D’Souza, CRNP, Rebecca Hommer, MD, Liliya Katsovich, MA, Robert A. King, MD, James F. Leckman, MD, Phd
Journal of the American Academy of Child & Adolescent Psychiatry–2016

IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted.