Publications by authors named "Michael Cooperstock"

12 Publications

  • Page 1 of 1

Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms.

J Neuroimmunol 2020 02 15;339:577138. Epub 2019 Dec 15.

Moleculera Labs, Inc., 755 Research Parkway, Suite 410, Oklahoma City, OK 73104, United States of America.

Objective: This retrospective study examined whether changes in patient pre- and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS).

Methods: In an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre- and post-treatment symptoms. Clinician and parent-reported symptoms after treatment or medical intervention were categorized as "Improved/Resolved" (n = 34) or "Not-Improved/Worsened" (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability.

Results: Comparison of pre- and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 (p < 1.67 × 10) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays.

Conclusion: This study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneuroim.2019.577138DOI Listing
February 2020

Palatal Petechiae in the Absence of Group A Streptococcus in Pediatric Patients with Acute-Onset Neuropsychiatric Deterioration: A Cohort Study.

J Child Adolesc Psychopharmacol 2017 Sep 7;27(7):660-666. Epub 2017 Apr 7.

1 Divisions of Pediatric, Department of Allergy, Immunology, and Rheumatology, Palo Alto, California.

Background: Palatal petechiae are 95% specific for streptococcal pharyngitis. Despite this, and despite prior research demonstrating that Group A Streptococcus (GAS) is a common antecedent to pediatric acute-onset neuropsychiatric syndrome (PANS) episodes, we anecdotally observed a low rate of documented GAS in patients with PANS and palatal petechiae. This retrospective chart review was conducted to formally report the rate of palatal petechiae and concurrent GAS in a cohort of patients with PANS and investigate other etiologic factors.

Methods: The clinical notes of 112 patients seen at the Stanford PANS Clinic who met PANS research criteria were reviewed for mention of palatal petechiae. The medical records of patients who demonstrated palatal petechiae on physical examination were reviewed for signs of infection, a clinical history of trauma, and laboratory results that could indicate other causes of petechiae.

Results: Twenty-three patients had documented palatal petechiae on physical examination (ages 5-16, 13/23 [57%] male). Fifteen patients had a rapid GAS test and GAS culture in the Stanford PANS clinic, all with negative results. Evidence of recent GAS infection was found in 8/23 (32%) patients (elevated GAS titers [n = 6] or documentation of a positive rapid GAS test at another facility [n = 2]), one of whom also had potential herpes simplex virus (HSV) infection. One patient had potential HSV infection and recent palatal trauma. No patients had thrombocytopenia. 14/23 (61%) of patients with palatal petechiae had no discernable cause of petechiae. 10/19 (53%) of patients had antihistone antibodies.

Conclusions: Despite the established relationship between palatal petechiae and GAS, no patient with palatal petechiae in our clinic tested positive for GAS and only 32% had evidence of recent GAS. Most did not have an identifiable cause for the palatal lesions. This finding suggests the potential for alternative causes of palatal petechiae or undetectable GAS in our patient population. The high prevalence of palatal petechiae without GAS infection suggests that the pathogenesis of PANS is multifactorial and may involve disruption or inflammation of the microvasculature. Additional research is needed to further elucidate these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/cap.2016.0153DOI Listing
September 2017

Looking for PANDAS in Missouri.

Mo Med 2017 Mar-Apr;114(2):125-128

Michael P. Sherman, MD, PhD, is in the Division of Neonatology in the Department of Child Health, University of Missouri - Columbia School of Medicine.

This review seeks to educate clinicians and advocate for patients having acute-onset pediatric autoimmune encephalopathy. Primary care providers caring for children are not fully aware of the debilitating illness that changes the life of a child and a family overnight. Our goal is to heighten awareness of a) the initial diagnosis, b) treatment and c) information about referral of affected children by health professionals in Missouri and surrounding states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140031PMC
September 2018

Household Clustering of Sequence Type 131 Clinical and Fecal Isolates According to Whole Genome Sequence Analysis.

Open Forum Infect Dis 2016 Sep 16;3(3):ofw129. Epub 2016 Jun 16.

George Washington University , Washington, District of Columbia.

 Within-household sharing of strains from the resistance-associated 30R1 and 30Rx subclones of sequence type 131 (ST131) has been inferred based on conventional typing data, but it has been assessed minimally using whole genome sequence (WGS) analysis.  Thirty-three clinical and fecal isolates of ST131-30R1 and ST131-30Rx, from 20 humans and pets in 6 households, underwent WGS analysis for comparison with 52 published ST131 genomes. Phylogenetic relationships were inferred using a bootstrapped maximum likelihood tree based on core genome sequence polymorphisms. Accessory traits were compared between phylogenetically similar isolates.  In the WGS-based phylogeny, isolates clustered strictly by household, in clades that were distributed widely across the phylogeny, interspersed between 30R1 and 30Rx comparison genomes. For only 1 household did the core genome phylogeny place epidemiologically unlinked isolates together with household isolates, but even there multiple differences in accessory genome content clearly differentiated these 2 groups. The core genome phylogeny supported within-household strain sharing, fecal-urethral urinary tract infection pathogenesis (with the entire household potentially providing the fecal reservoir), and instances of host-specific microevolution. In 1 instance, the household's index strain persisted for 6 years before causing a new infection in a different household member.  Within-household sharing of ST131 strains was confirmed extensively at the genome level, as was long-term colonization and repeated infections due to an ST131-30Rx strain. Future efforts toward surveillance and decolonization may need to address not just the affected patient but also other human and animal household members.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047392PMC
http://dx.doi.org/10.1093/ofid/ofw129DOI Listing
September 2016

Anti-neural antibody response in patients with post-treatment Lyme disease symptoms versus those with myalgic encephalomyelitis/chronic fatigue syndrome.

Brain Behav Immun 2015 Aug 10;48:354-5. Epub 2015 Apr 10.

Department of Medicine, Columbia University Medical Center, 1130 Saint Nicholas Ave., Room 937, New York, NY 10032, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2015.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638178PMC
August 2015

Interactions of phthalates with preterm birth.

Environ Int 2015 Apr 19;77:160. Epub 2015 Jan 19.

Division of Infectious Diseases, Department of Child Health, University of Missouri Health Care, Columbia, MO 65212, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2014.10.021DOI Listing
April 2015

Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference.

J Child Adolesc Psychopharmacol 2015 Feb 17;25(1):3-13. Epub 2014 Oct 17.

1 Professor of Psychiatry, Director of the Pediatric Bipolar Disorders Program, Stanford University School of Medicine , Stanford, CA.

On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/cap.2014.0084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340805PMC
February 2015

Altered neutrophil counts at diagnosis of invasive meningococcal infection in children.

Pediatr Infect Dis J 2013 Oct;32(10):1070-2

From the *University of Missouri School of Medicine, Columbia, MO; †Department of Pediatrics, Pediatric Infectious Disease Section, Baylor College of Medicine, Houston, TX; ‡Department of Pediatrics, University of Arkansas of Medical Sciences, Little Rock, AR; §Department of Pediatrics, Children's Hospital San Diego, San Diego, CA; ¶Department of Pediatrics, Ohio State University College of Medicine and Public Health, Columbus, OH; ‖Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN; **Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, UT; ††Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC; ‡‡Department of Pediatrics, Northwestern University Medical School, Chicago, IL; §§Department of Pediatrics, University of Southern California School of Medicine, Los Angeles, CA; ¶¶Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA; ‖‖Department of Pediatrics, Pediatric Infectious Disease Section, Baylor College of Medicine, Houston, TX; and ***Department of Child Health, Division of Infectious Disease and Rheumatology, University of Missouri School of Medicine, Columbia, MO.

Background: Invasive meningococcal infections can be devastating. Substantial endotoxemia releases mature and immature neutrophils. Endothelial margination of mature neutrophils may increase the immature-to-total neutrophil ratio (ITR). These changes have not been previously well-described in invasive meningococcal disease.

Methods: Using 2001 to 2011 data from the US Multicenter Meningococcal Surveillance Study, the diagnostic sensitivity and clinical correlates of white blood cell count, absolute neutrophil count (ANC), immature neutrophil count (INC) and ITR were evaluated alone and in combination at the time of diagnosis of invasive meningococcal disease.

Results: Two hundred sixteen patients were evaluated: meningococcemia (65), meningitis (145) and other foci (6). ANC ≤1000/mm(3) or ≥10,000/mm(3) was present in 137 (63%), INC ≥500/mm(3) in 170 (79%) and ITR ≥0.20 in 139 (64%). One or more of these 3 criteria were met in 204 of the 216 (94%). Results were similar for meningococcemia and meningitis subgroups. All 13 cases with mildest disease met 1 or more of the 3 criteria. Eight children presented with ANCs <1000/mm(3): 3 of them died and a fourth required partial amputation in all 4 limbs.

Conclusions: Invasive meningococcal disease is characterized by striking abnormalities in ANC, INC and/or ITR. Neutropenia was associated with a poor prognosis. Notably, without INCs, 37% of cases would have been missed. Automated methods not measuring immature white blood cells should be avoided when assessing febrile children. Serious infection should be considered when counts meet any of the 3 criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0b013e31829e31f1DOI Listing
October 2013

The neonatal group B streptococcal epidemic: lessons learned from studying associations.

Neonatology 2011 18;100(4):409-11. Epub 2011 Oct 18.

Neonatology Fellowship, Division of Neonatology, Columbia, MO 65201, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000329538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701447PMC
March 2012

Isolation of Exophiala dermatitidis from pigmented sputum in a cystic fibrosis patient.

Pediatr Pulmonol 2010 May;45(5):508-10

University of Missouri, Columbia, Missouri, USA.

A 16-year-old female with cystic fibrosis (CF) presented with an acute respiratory exacerbation during which black flecks were observed in the spontaneously expectorated sputum. The production of this pigmented sputum was subsequently attributed to Exophiala dermatitidis hyphae. Treatment with antibiotics, corticosteroids, and antifungal medications led to an initial resolution of symptoms and clearance of the black pigment from her sputum. However, the patient again presented nine months later with reappearance of the pigmented flecks and concomitant clinical deterioration and was subsequently treated with an extended course of voriconazole. To the authors' knowledge, this is the first case report of fungal colonization by E. dermatitidis presenting as black flecks spontaneously expectorated in CF sputum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.21187DOI Listing
May 2010

Within-household sharing of a fluoroquinolone-resistant Escherichia coli sequence type ST131 strain causing pediatric osteoarticular infection.

Pediatr Infect Dis J 2010 May;29(5):473-5

Infectious Diseases Section, Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.

A fluoroquinolone-resistant Escherichia coli strain of sequence type ST131 caused severe septic arthritis and contiguous osteomyelitis in an 8-month-old girl, and colonized the girl's healthy mother, who shared a different fecal E. coli strain with the father. Within-household transmission can contribute to the dissemination of the emerging, multidrug-resistant ST131 clonal group, which has evident invasive potential for otherwise-healthy children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0b013e3181c89bd7DOI Listing
May 2010

Causes of infant mortality at night.

J Pediatr 2004 Jul;145(1):141-2; author reply 142

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2004.03.038DOI Listing
July 2004