Global Disease Data

Delivered March 26th, 2019. Contributors: Dagmawit W., Sameen B., Michelle A., Eunice O. and

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Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)

 This spreadsheet has been populated with information that this research was able to obtain. A small data set of self-reports from 700 families has been used to provide estimates as this is a rare disease. The onset age prevalence, mentions of some centers of excellence, and various aspects of the disease are provided below, together with the research strategies for the parts of the question that were not answered.
MethodologyThe research strategies we attempted in search of relevant information to populate the spreadsheet are outlined below.

First, we searched through US government health-commissioning databases and websites as well as global organizations for any study or research that may have been mentioned. These sites include WHO, NIH, ClinicalTrials, and NCBI reports. Unfortunately, we only found descriptive information about PANS, its symptoms, causes, and treatments. We used the findings to populate the "treatment" column.

Our second strategy involved consulting several research studies and medical sources such as Researchgate.net, OMICS International, Stanford Medicine, and Psychiatric Advisor. We searched for any publicly available report of PANS within the past 5 or 10 years. However, we could not find any relevant information on the same. The only information we captured from one source stated that there hasn’t been a large population study on the incidence of PANS or PANDAS but they were able to estimate the US prevalence of the disease at one in 200 children. The statistics provided on this site were based on 700 family self-reports. Because this disease is rare, we used this data to populate the spreadsheet.

Our third strategy involved searching through PANS associations for any treatment protocols in development, centers of excellence, and diagnostic guidelines. While on the center of excellence, we searched for hospitals and research facilities taking the lead on treatment of PANS. This research revealed Pace Foundation, a nonprofit based in Arizona and is geared toward improving the diagnosis and treatment of patients with this condition and CPAE Center of Excellence as one of the clinical services in the University of Arizona health sciences that "implements an integrated model of basic science and clinical research, clinical care, and education to address a spectrum of neuropsychiatric disorders that are often misdiagnosed, under diagnosed, or undiagnosed in children." Using the information acquired here, we populated the "Excellence Centers" column.

This research could not provide global data for PANS incidence because this is a rare disease and there are limited studies that have been conducted. Nonetheless, the research was able to determine different aspects of the disease prevalence and basic information on the centers of excellence. The data of these findings are provided below, and in this spreadsheet as well.
PEDIATRIC ACUTE-ONSET NEUROPSYCHIATRIC SYNDROME (PANS)The PANS disease is "a condition defined by sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms."
PANS describes all OCD cases that consist of acute-onset cases while PANDAS are PANS cases that have streptococcal infections. When comparing the two, PANS is the general umbrella while PANDAS is one specific part under it. To understand this better, PANS is like Cancer as PANDAS is like Leukemia. Typically, PANS symptoms begin at childhood.
CURRENTLY AVAILABLE TREATMENTSThe type of treatment recommended is highly dependent on various factors: the symptoms, severity of the condition, and if identifiable, the cause. When analyzing the symptoms, the one that most severely affects the day to day of an individual may determine the type of treatment one will receive.

These are the current available treatment of PANS:
1. Use of Psychiatric medications to treat specific symptoms, psychotherapy, and supportive interventions.
2. Antibiotics to treat any underlying infections or inflammations.
3. Immunotherapy or anti-inflammatory therapy may be critical in ensuring the stability of the immune system.
CENTERS OF EXCELLENCEThe Children's Postinfectious Autoimmune Encephalopathy (CPAE) Center of Excellence at the UA Steele Center partnered with Banner-University Medicine and the NIH/NIMH to implement an "integrated model of basic science and clinical research, clinical care and education to address a spectrum of neuropsychiatric disorders that are often misdiagnosed, underdiagnosed or undiagnosed in children." Pace Foundation is a nonprofit organization in Arizona that aims to improve the diagnosis and treatment of patients with PANS.
STATISTICS Dr. Susan E. Swedo, M.D., FAAP, chief of the Pediatrics and Developmental Neuroscience Branch at the National Institute of Mental Health (NIMH) stated that there is no incidence data on PANS yet. She estimates that the disorder impacts about 1% of elementary school-aged children and this is likely under diagnosed. PANDAS Physicians Network (PPN) maintains a diagnostic algorithm on its website as well as treatment guidelines.

In the US, there is a prevalence conservative estimate of 1 in 200 children, however, the true lifetime prevalence of PANDAS or PANS is not known. In the US, approximately 500,000 children under 18 have OCD. Based on an analysis of 700 family self-reports, 4 to 9 years has the highest age onset with 69%. During primary symptoms, the OCD is at 37% and TICS has 14% with both combined percentage of 49%. The PANDAS/PANS population demographic shows that overview has young age onset of Tics is 6.5 years with an allowance of two years, and 7.4 years with a two-year allowance for OCD. For those over eight years old, the ratio for boys to girls is 2.6:1; while those below, the ratio of boys to girls is 4.7:1.
 

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Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

According to estimates, 1 in 200 children in the United States suffers from Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections, also called PANDAS. We have compiled the requested details on currently available treatments, treatment protocols in development, centers of excellence, and diagnostic guidelines for PANDAS in the attached spreadsheet.
METHODOLOGY
We were unable to locate the 5-year and 10-year historical incidence of PANDAS globally and in the United States. The following research strategies were attempted in search of the required information: 

We started our research by scouring through health and medical research websites and databases including the National Institutes of Health, U.S. Department of Health & Human Services, NCBI, ResearchGate, WHO, ClinicalTrials, etc. to find any studies or reports indicating the incidence or prevalence of the disease over the past 5 or 10 years. However, no such information was available given the rarity of the disease. During our research, most of the studies we came across were focused on the treatments of PANDAS. 

We then ran a press scan to find any news reports or articles indicating the incidence or prevalence of PANDAS in the U.S. or around the world. We also tried searching for the number of reported cases of PANDAS but this approach was also unsuccessful. However, we did find the recent estimated incidence/ prevalence of PANDAS (1 in 200 children) across various sources.  

As our next strategy, we looked for specific organizations and centers of excellence related to PANDAS hoping to find the incidence data. We found several helpful resources such as PANDAS Network and PNN among others. However, no historic incidence data for PANDAS could be retrieved from these sources. 
RECENT INCIDENCE AND PREVALENCE IN THE US
Although being an extremely rare disease the actual prevalence and incidence of PANDAS are unknown, it is estimated that 1 in 200 children in the United States suffers from PANDAS. 
RECENT INCIDENCE AND PREVALENCE WORLDWIDE
Some research studies, which are only accessible with subscription plans, report that the annual incidence of PANDAS "ranges between 0 per 10,000 cultures to 10 per 30,000 cultures" (1 in 3,000), depending upon certain factors. However, despite PANDAS being a rare disease, some researchers claim that PANDAS account for ≥10% of childhood tic disorder and obsessive-compulsive disorder (OCD). In an interview to Cosmopolitan in 2014, a neurologist Dr. Rosario Trifiletti from New Jersey claimed that he treated 3,000 PANDAS cases in 5 years. Because we could not access these researches, we assumed their incidence rate as global PANDAS incidence rate. 
HISTORIC INCIDENCE AND PREVALENCE IN THE US
While no information was found on the 5-year or 10-year incidence rate of PANDAS, we located some maps prepared by the PANDAS Network showing 2806 self-reported PANDAS/PANS cases in the United States through 2015. 

We also found that in 2010, the PANDAS Network published a list of 200 random PANDAS cases from a total of 600 cases where the reported onset years of PANDAS were between 1996 to 2010. We decided to sum up the number of cases in each year from 2000 to 2009 from the sample of 200 cases to look for an increasing or decreasing trend in the number of reported cases over the decade. This approach indicated an increasing trend in the incidences (number of cases) of PANDAS reported over the years. 

 2000: 0  
  2001: 2  
  2002: 1  
  2003: 4  
  2004: 8  
  2005: 10  
  2006: 14  
  2007: 20  
  2008: 39  
  2009: 48 

Because there was no other data available, we used this as a proxy to conclude that the incidence of PANDAS in the U.S. is increasing year by year. 

The remaining information regarding the currently available treatments, treatment protocols in development, centers of excellence, and diagnostic guidelines for PANDAS in the attached spreadsheet. 

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Sydenham’s Chorea

While publicly available data did not allow us to provide all the requested details on Sydenham chorea, we were able to provide most of the information. "Sydenham chorea (SC) is a neurological disorder of childhood resulting from infection via Group A beta-hemolytic streptococcus (GABHS), the bacterium that causes rheumatic fever." The disease is exceptionally rare in the U.S., and it was estimated that in or around 1999, there were between 2,876 and 4,314 cases. Our findings are provided in the attached spreadsheet. Below we explain any missing data, as well as provide calculations for the estimated data. 
Incidence of Sydenham's ChoreaWe initially looked for data on the prevalence of Sydenham chorea in publicly available databases such as the Centers for Disease control and the World Health Organization. The NCBI indicated in a report updated in 2019 that "...the global incidence of chorea is lacking."  This confirmed that the statistics would likely not be available.

While we were unable to locate statistics in databases, we did find data indicating that SC is a result of the rheumatic fever bacteria. We searched for more data on the connection between the two diseases and found two relevant statistics.
According to the National Center for Biotechnology Information, up to 40% of patients with rheumatic fever will get SC. 
The National Organization for Rare Disorders states that about 25% of rheumatic fever sufferers will get SC.
Based on the difference in these two stats, we decided to use the average of the two in our estimates. So we assumed 40 + 25)/2 = 37.5% of rheumatic fever sufferers will get SC.

We proceeded to look for both global and U.S. data on the incidence of rheumatic fever. While we were able to locate some information, the U.S. data was from the end of the 20th century (we assumed about 1999), and the global data was from 2005. Because the data was already older than the 5-10 year historical data requested, we have only provided the most recent incidence data. The historical data is marked N/A in the attached spreadsheet. It is likely that the relative rarity of SC in the U.S. is the reason that statistics on the prevalence of it are not consistently tracked.

GLOBAL
A 2015 CDC report indicated that the global incidence of acute rheumatic fever in 2011 was 1.1 cases per 1,000 children under age 18. It was 1.5 cases per 1,000 in 2012.
Although we tried to find the total global population for children under 18 in 2011 or 2012, much of the data available was segmented into a 0-14 bracket and a 15-24 bracket. This did not allow us to pull the data we needed for the total world population that was under age 18. Our hope was that we could estimate the number of case of rheumatic fever in 2011 or 2012 and then use that to estimate the number of cases of SC.
We did find a statistic from a 2005 report that indicated there were 470,000 new cases of acute rheumatic fever globally each year.
 470,000 * 37.5% (percent of rheumatic fever sufferers who get SC) = 176,250 global cases of SC per year in 2005.

UNITED STATES
The 2015 CDC report also indicated that at the end of the 20th century, the U.S. incidence of acute rheumatic fever was between .04-.06 cases per 1,000 children. The population of children under age 18 in the U.S. in 1999 was 71.9 million. Therefore:
71.9 million children/1000*.04 = 2,876
71.9 million children/1000*.06 = 4,314
So at the end of the 20th century, we assumed 1999, the incidence of acute rheumatic fever in the United States was estimated to be between 2,876 and 4,314 cases.
The estimated number of cases of Sydenham chorea is between 1,079 and 1,618 [2876*37.5%=1,079 and 4314*37.5%=1,618].

The remaining data requested on currently available treatments, treatment protocols in development, centers of excellence, and diagnostic guidelines was available and has been included in the attached spreadsheet.

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Autoimmune Encephalitis (AE)

According to the study conducted by NCBI, the incidence rate from 1995 to 2005 was 0.4 per 100,000 persons and 1.2 per 100,000 persons from 2006 to 2015. The increase is due to improved detection of autoantibody-positive cases. The autoantibodies with high specificity of AE were ANNA1, ANNA2, ANNA3, amphiphysin, AMPA, DPPX, among others. More details are in the attached spreadsheet. 
METHODOLOGYWe leveraged medical and health reports, and articles on Autoimmune Encephalitis from relevant and credible sources like NHLBI, Sagepub, Journal watch, Clinical Trial, Autoimmune Encephalitis Alliance, among others. We were able to locate useful information that helped us to answer the client's question. However, during our search, we were unable to identify sources that provided the most recent U.S. incidence information in terms of a specific year. But, we found a date range of 1995 to 2005 and 2006 to 2015. We, therefore, took date the range of 2006 to 2015 as our most recent data.

We then proceeded to search for recent, five-year, and ten-year global incidences from international sources like the World Health Organization, Encephalitis Society, International Autoimmune Encephalitis Society, GARD, among others. However, we were unable to locate the most recent Global incidence data in terms of a specific current year. Fortunately, we found an article on the Autoimmune Encephalitis Alliance website that provided an overview of the Mayo Study on AE. The article equates the incidence rate of 1.2 per 100,000 to 4000 annual new cases in the United States and 90,000 new yearly cases globally from 2006 to 2015. The date range from 2006 to 2015 covers the ten-year and five-year historical incidences as requested. 
CALCULATIONThe date range from 2006 to 2015 covers the ten-year and five-year historical incidences as requested. Therefore, from this given information we assumed that the recent U.S. and global incident data are 4000 incidences and 90,000 incidences respectively. We then calculated the five-year and ten-year U.S. incidence as follows;

U.S. five-year data is 4000x5= 20,000 incidences,
U.S. ten-year- data were 4000 x 10= 40,000 incidences.

For the global incidence, we made the following assumptions and calculations

Recent global incidence = 90,000
Five year global data = 90,000 x 5= 450,000 incidences
Ten year global data = 90,000 x 10 = 900,000 incidences
MOST RECENT U.S. & Global INCIDENCE DATAAccording to the study conducted by NCBI, in the U.S., the most recent incidence data ranges from 2006 to 2015 and at a rate of 1.2 per 100,000 persons. A recent study by Mayo clinic estimated the recent incidence at 4,000 in the U.S. On the other hand, the study by Mayo Clinic estimated the recent global incidences to be approximately 90,000 new cases.
5-YEAR HISTORICAL U.S. & global INCIDENCEThe study by Mayo Clinic estimated the 5-year historical U.S. incidence to be 4000 x 5 = 20,000 while the 5-year historical global incidence rate was estimated at 90,000 x 5 = 450,000 new cases.
10-YEAR HISTORICAL U.S. & global INCIDENCEAccording to research carried and published by Mayo Clinic AE experts, in the last ten years, there were approximately 4000 x 10= 40,000 new cases of AE in the United States. Moreover, the study estimated the 10-year historical incidence at approximately 90,000 x 10= 900,000 new cases globally.
CURRENTLY AVAILABLE TREATMENTS
 Corticosteroids are used in the treatment of AE to inhibit the inflammatory process. However, it has various systematic side effects.

Under first line immunotherapy, there are three therapies currently offered — first, the removal of teratoma. Second, Methylprednisolone — Regimen: 1g is administered daily for 3 to 5 days. Third, intravenous immunoglobin — 2g/kg is administered for over five days. And lastly, plasma exchange/immunoadsorption occurs one session every other 5 to 7 cycles.

Under second line immunotherapy, Rituximab — 375mg is administered weekly as an infusion of IV for four weeks. Also, Cyclophosphamide -750mg is administered monthly for 3 to 6 months.

Under alternative therapy, Tocilizumab — is administered. The first dose prescribed should be 4mg then followed by 8mg per month depending on clinical response. Alternatively, low dose interleukin 2:1.5 million IU is administered per day, and four subcutaneous injections at an interval of three weeks.

Also, steroid-sparing agents can be used for maintenance therapy and include Azathioprine; initially 1-1.5 mg administered once a day then followed by two to 3 mg/kg per day. Lastly, Mycophenolate mofetil 500 mg can as well be administered twice a day.
TREATMENT PROTOCOLS IN DEVELOPMENT
 Immunotherapy in Autoimmune: The treatment procedure involves plasma exchange. The drugs to be administered are high-dose glucocorticoid and plasma exchange. This trial involves exploring the effects of treatment and long-term prognosis by comparing plasma exchange (PE) joined with medication therapy to plasma exchange after medication immunotherapy in AE patients. This trial aims to make it clear that plasma exchange in the early stage of treatment can be more effective than PE after treatment. According to this trial, the selected patients with AE will receive symptomatic, immunotherapy, supportive treatment, and tumor screening. The study is only eligible to AE students who are 14 to 65 years.

CENTERS OF EXCELLENCE
Bostons Children's Hospital
 Boston Children’s Hospital is one of the hospitals in the United States that provides childhood treatment including autoimmune encephalitis.

Johns Hopkins
Located in Maryland, Johns Hopkins is a hospital that provides inpatient services on neurology and neurosurgery. The hospital is also one of the providers of AE treatment.

Mayo Clinic
 Mayo Clinic has a team of medical experts who specializes in brain and nervous system, brain imaging, and infectious diseases.

Great Ormond Street Hospital For Children
Formed in 1982, Great Ormond Street Hospital for Children is a child healthcare center. The hospital is committed to finding better and new ways of treating childhood illness including autoimmune encephalitis.
DIAGNOSTIC GUIDELINES
If there is the existence of a subacute onset of working memory deficit, psychiatric symptoms, or altered mental status. When there is at least one of these: seizures not explained by a previously known seizure disorder, MRI shows suggestive encephalitis or CSF pleocytosis. And when there is a reasonable exclusion of alternative causes of autoimmune encephalitis.

Sources

From Part 01

PANDAS/PANS treatments, awareness evolve, but some experts skeptical

aappublications.org

Publication Year: 2017

Quotes

"The term PANDAS was coined in the 1980s by Susan E. Swedo, M.D., FAAP, chief of the Pediatrics and Developmental Neuroscience Branch at the National Institute of Mental Health (NIMH), after she discovered a link between abrupt-onset obsessive-compulsive disorder (OCD) and group A Streptococcus (GAS)."
"PANDAS is a subset of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), which has the same symptoms but can be caused by infections like varicella or influenza, she said."

PANS: Pediatric Acute-onset Neuropsychiatric Syndrom | Q & A

med.stanford.edu

Publication Year: 2019

Quotes

"There hasn’t been a large population study on the incidence of PANS or PANDAS, so we don’t know how common they are. PANS and PANDAS are often overlooked by medical doctors because of the assumption that there is not an underlying medical cause for the patient’s psychiatric symptoms."

Information About PANS/PANDAS

nimh.nih.gov

Publication Year: 2019

Quotes

"Since PANS is newly described, research is ongoing to determine which interventions will be effective. If the diagnostic work-up of PANS reveals an infectious trigger, treatment of the infection may be useful in reducing symptom severity of the OCD and other neuropsychiatric symptoms. The following treatment information is directed at PANDAS, since that is where the research has been done, but may prove useful for PANS, as well."

Statistics | PANDAS Network

pandasnetwork.org

Publication Year: 2019

Pediatric acute-onset neuropsychiatric syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program

rarediseases.info.nih.gov

Welcome to the Children’s Postinfectious Autoimmune Encephalopathy (CPAE) Center of Excellence

peds.arizona.edu

Pace Foundation

pacefoundation4kids.org

Global Disease Data

docs.google.com

Publication Year: 2019

From Part 02

Global Disease Data

docs.google.com

Publication Year: 2019

Living with PANDAS, a childhood tragedy

kdrv.com

Publication Year: 2019

Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program

rarediseases.info.nih.gov

Publication Year: 2018

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Strept

prweb.com

Publication Year: 2019

Statistics | PANDAS Network

pandasnetwork.org

Publication Year: 2019

PANDAS: A Rare Disease? Or Not a Disease at All?

undark.org

Publication Year: 2017

MAP OF CASES (2015 & 2011)

pandasnetwork.org

200 P.A.N.D.A.S. Cases from PandasNetwork.org

pandasnetwork.org

UpToDate

uptodate.com

Publication Year: 2019

From Part 03

Sydenham Chorea Information Page | National Institute of Neurological Disorders and Stroke

ninds.nih.gov

Publication Year: 2019

Chorea, Sydenham - StatPearls - NCBI Bookshelf

ncbi.nlm.nih.gov

Publication Year: 2018

Quotes

"SD is much less common today than in the past, but when it does occur, the symptoms are less severe and the relapses are less frequent. This may be partially due to aggressive treatment of Group A Streptococcal infections, improved general hygiene practices, and a reduction in the strain of Gp A Streptococcus that causes the antigenic mimicry that triggers the disease."

Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Volunteers - Full Text View - ClinicalTrials.gov

clinicaltrials.gov

Publication Year: 2019

Intravenous Immunoglobulins as Effective Treatment in Sydenham’s Chorea - Full Text View - ClinicalTrials.gov

clinicaltrials.gov

Sydenham Chorea - NORD (National Organization for Rare Disorders)

rarediseases.org

Chorea - StatPearls - NCBI Bookshelf

ncbi.nlm.nih.gov

Publication Year: 2019

Acute Rheumatic Fever and Rheumatic Heart Disease Among Children — American Samoa, 2011–2012

cdc.gov

Publication Year: 2015

POP1 Child population: Number of children (in millions) ages 0–17 in the United States by age, 1950–2017 and projected 2018–2050

childstats.gov

Publication Year: 2018

2018 World Population Data Sheet With Focus on Changing Age Structures – Population Reference Bureau

prb.org

Publication Year: 2018

Group A Strep | Acute Rheumatic Fever | For Clinicians | GAS | CDC

cdc.gov

Publication Year: 2018

Welcome to the Children’s Postinfectious Autoimmune Encephalopathy (CPAE) Center of Excellence

peds.arizona.edu

Quotes

"The Children's Postinfectious Autoimmune Encephalopathy (CPAE) Center of Excellence at the UA Steele Center, developed in partnership with Banner-University Medicine and in cooperation with the NIH/NIMH is the first in the U.S. to implement an integrated model of basic science and clinical research, clinical care and teaching to address a spectrum of neuropsychiatric disorders that are often misdiagnosed, underdiagnosed or undiagnosed in children."

Movement Disorder Treatments and Services

columbianeurology.org

Quotes

"The Division of Movement Disorders has been designated a Center of Excellence by the Parkinson Foundation (PF) (link is external). This award acknowledges our excellence and leadership in research, comprehensive care, professional education, and patient outreach. In addition to the latest medications and treatments, our center also offers comprehensive support services to improve your quality of life."
"As nationally and internationally renowned experts in the field of Parkinson's disease and other movement disorders, in terms of both our clinical activities and our cutting-edge research program, we are often called upon to educate future leaders in the field. The presence of postdoctoral fellows on our practice team serves to enhance the patient care experience, since "teaching moments" frequently benefit patients' as much as students, in terms of gaining a greater understanding of their disorder."