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Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS): Clinical Manifestations, IVIG Treatment Outcomes, Results from a Cohort of Italian Patients

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.

 

A Double-Blind Randomized Placebo-Controlled Pilot Study of Azithromycin in Youth with Acute-Onset Obsessive-Compulsive Disorder

Murphy, Brennan, Johnco, Parker-Athill, Miladinovic, Storch, Lewin 
J Child Adolesc Psychopharmacology-2017

This double blind pilot study suggests that azithromycin may be helpful in treating youth meeting the PANS diagnosis, especially those with elevated levels of both OCD and tic symptoms. Azithromycin was well tolerated, but the potential for cardiac risks suggests that additional monitoring may be needed to ensure safety.

Treatment of Pediatric Acute-Onset Neuropsychiatric Disorder in a Large Survey Population

Denise Calaprice, Janice Tona, and Tanya K. Murphy
Journal of Child and Adolescent Psychopharmacology-2017

Among the PANS patients represented in this study, relatively aggressive treatment courses targeted at eradicating infection and modulating the inflammatory response appeared to provide the best caregiver-reported therapeutic results, and to be generally well tolerated. Given its relative efficacy and tolerability, treatment targeting the inflammatory response may represent an underutilized approach in this population.

Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder

Sophia Attwells, HBS; Elaine Setiawan, PhD; Alan A. Wilson, PhD, Pablo M. Rusjan, PhD; Romina Mizrahi, MD, PhD, FRCP(C); Laura Miler, HBS; Cynthia Xu, MD; Margaret Anne Richter, MD, FRCP(C); Alan Kahn, MD, FRCP(C); Stephen J. Kish, PhD; Sylvain Houle, MD, PhD, FRCP(C); Lakshmi Ravindran, MD, FRCP(C); Jeffrey H. Meyer, MD, PhD, FRCP(C)
JAMA Psychiatry 2017

The regional distribution of elevated TSPO VT argues that the autoimmune/neuroinflammatory theories of OCD should extend beyond the basal ganglia to include the cortico-striato-thalamo-cortical circuit. Immunomodulatory therapies should be investigated in adult OCD, rather than solely childhood OCD, particularly in cases with prominent distress when preventing compulsions.

Mental Health News Article
Brain Behavior Research Foundation Article

Association of Streptococcal Throat Infection With Mental Disorders Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study

Sonja Orlovska, Claus Høstrup Vestergaard, Bodil Hammer Bech, PhD
JAMA Psychiatry-2017

This large-scale study investigating key aspects of the PANDAS hypothesis found that individuals with a streptococcal throat infection had elevated risks of mental disorders, particularly OCD and tic disorders. However, nonstreptococcal throat infection was also associated with increased risks, although less than streptococcal infections for OCD and any mental disorder, which could also support important elements of the diagnostic concept of pediatric acute-onset neuropsychiatric syndrome.

Effect of Early and Prophylactic Nonsteroidal Anti-Inflammatory Drugs on Flare Duration in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Observational Study of Patients Followed by an Academic Community-Based Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic

Brown Kayla D., Farmer Cristan, Freeman G. Mark Jr., Spartz Ellen J., Farhadian Bahare, Thienemann Margo, and Frankovich Jennifer
JCAP-July 2017

NSAIDs given prophylactically or within 30 days of flare onset may shorten neuropsychiatric symptom duration in patients with new-onset and relapsing/remitting PANS and PANDAS. A randomized placebo-control clinical trial of NSAIDs in PANS is warranted to formally assess treatment efficacy.

Course of Neuropsychiatric Symptoms After Introduction and Removal of Nonsteroidal Anti-Inflammatory Drugs: A Pediatric Observational Study

Spartz Ellen J., Freeman G. Mark Jr., Brown Kayla, Farhadian Bahare, Thienemann Margo,Frankovich, Jennifer
JCAP-July 2017

Improvement in neuropsychiatric symptoms was evident in roughly one-third of NSAID treatment trials. A randomized clinical trial will be necessary to confirm whether NSAIDs are successful in reducing neuropsychiatric symptoms in youth with PANS.

Pediatric Acute-Onset Neuropsychiatric Syndrome Response to Oral Corticosteroid Bursts: An Observational Study of Patients in an Academic Community-Based PANS Clinic

Brown Kayla, Farmer Cristan, Farhadian Bahare, Hernandez Joseph, Thienemann Margo, and Frankovich Jennifer
JCAP-2017

Corticosteroids may be a helpful treatment intervention in patients with new-onset and relapsing/remitting PANS and PANDAS, hastening symptom improvement or resolution. When corticosteroids are given earlier in a disease flare, symptoms improve more quickly and patients achieve clinical remission sooner. Longer courses of corticosteroids may result in more durable remissions. A double-blind placebo-controlled clinical trial of corticosteroids in PANS is warranted to formally assess treatment efficacy.

 

Clinical Management of PANS: Part II—Use of Immunomodulatory Therapies

Frankovich Jennifer, Swedo Susan, Murphy Tanya, Dale Russell C., Agalliu Dritan, Williams Kyle, Daines Michael, Hornig Mady, Chugani Harry, Sanger Terence, Muscal Eyal, Pasternack Mark, Cooperstock Michael, Gans Hayley, Zhang Yujuan, Cunningham Madeleine, Bernstein Gail, Bromberg Reuven, Willett Theresa, Brown Kayla, Farhadian Bahare, Chang Kiki, Geller Daniel, Hernandez Joseph, Sherr Janell, Shaw Richard, Latimer Elizabeth, Leckman James, Thienemann Margo, and PANS/PANDAS Consortium
Journal of Child and Adolescent Psychopharmacology-2017
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These recommendations will help guide the use of anti-inflammatory and immunomodulatory therapy in the treatment of PANS.