Possible causes of sudden onset OCD in kids broadened

Criteria for a broadened syndrome of acute onset obsessive compulsive disorder (OCD) have been proposed by a National Institutes of Health scientist and her colleagues. The syndrome, Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), includes children and teens that suddenly develop on-again/off-again OCD symptoms or abnormal eating behaviors, along with other psychiatric symptoms – without any known cause.

PANS expands on Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS), which is limited to a subset of cases traceable to an autoimmune process triggered by a strep infection. A clinical trial testing an immune-based treatment for PANDAS is currently underway at NIH and Yale University (see below).

“Parents will describe children with PANS as overcome by a ‘ferocious’ onset of obsessive thoughts, compulsive rituals and overwhelming fears,” said Susan Swedo, M.D., of the NIH’s National Institute of Mental Health (NIMH), who first characterized PANDAS two decades ago. “Clinicians should consider PANS when children or adolescents present with such acute-onset of OCD or eating restrictions in the absence of a clear link to strep.”

Swedo, James Leckman, M.D., of Yale University, and Noel Rose, M.D., Ph.D. of Johns Hopkins University, propose working criteria for PANS in February 2012 in the open source journal Pediatrics & Therapeutics.

“As the field moves toward agreement on this broadened syndrome, affected youth will be more likely to receive appropriate care, regardless of whether they are seen by a neurologist, pediatrician or child psychiatrist,” said NIMH Director Thomas R. Insel, M.D.

Differing causes sharing a “common presentation”

The PANS criteria grew out of a PANDAS workshop convened at NIH in July 2010, by the NIMH Pediatric and Developmental Neuroscience Branch, which Swedo heads. It brought together a broad range of researchers, clinicians and advocates. The participants considered all cases of acute-onset OCD, regardless of potential cause.

Clinicians reported that evaluations of more than 400 youth diagnosed with PANDAS confirmed that affected boys outnumbered girls 2:1, with psychiatric symptoms, always including OCD, usually beginning before 8 years.

Although debate continues about the fine points, the field is now of one mind on the core concept of “acute and dramatic” onset of a constellation of psychiatric symptoms. There is also broad agreement on the need for a “centralized registry” that will enable the research community to analyze evidence from studies that will eventually pinpoint causes and treatments. Such a registry is currently under development by members of the International Obsessive Compulsive Foundation (IOCDF).

Since a diagnosis of PANS implies no specific cause, clinicians will have to evaluate and treat each affected youth on a case-by-case basis.

“PANS will likely turn out to include a number of related disorders with different causes that share a common presentation,” explained Swedo.

The authors propose that a patient must meet 3 diagnostic criteria for a diagnosis of PANS:

1. Abrupt, dramatic onset of OCD or anorexia.
2. Concurrent presence of at least two additional neuropsychiatric symptoms with similarly severe and acute onset. These include: anxiety; mood swings and depression; aggression, irritability and oppositional behaviors; developmental regression; sudden deterioration in school performance or learning abilities; sensory and motor abnormalities; somatic signs and symptoms.
3. Symptoms are unexplainable by a known neurologic or medical disorder.

Among the wide range of accompanying symptoms, children may appear terror stricken or suffer extreme separation anxiety, shift from laughter to tears for no apparent reason, or regress to temper tantrums, “baby talk” or bedwetting. In some cases, their handwriting and other fine motor skills worsen dramatically. Leckman’s team at the Yale Child Study Center is in the process of developing assessment tools for diagnosing the syndrome.

PANDAS treatment study targets errant antibodies

Meanwhile, Swedo, Leckman, and Madeleine Cunningham of the University of Oklahoma, and colleagues, are collaborating on a new, multi-site placebo-controlled study, testing the effectiveness of intravenous immunoglobulin (IVIG) for reducing OCD symptoms in children with PANDAS.

Previous human and animal research suggested mechanisms by which strep-triggered antibodies mistakenly attack specific brain circuitry, resulting in obsessional thoughts and compulsive behaviors.

“Strep bacteria has evolved a kind of camouflage to evade detection by the immune system,” Swedo explained. “It does this by displaying molecules on its cell wall that look nearly identical to molecules found in different tissues of the body, including the brain. Eventually, the immune system gets wise to this ‘molecular mimicry,’ recognizes strep as foreign, and produces antibodies against it; but because of the similarities, the antibodies sometimes react not only with the strep, but also with the mimicked molecules in the human host. Such cross-reactive ‘anti-brain’ antibodies can cause OCD, tics, and the other neuropsychiatric symptoms of PANDAS.”

IVIG, a medication derived from normal antibodies, neutralizes such harmful antibodies, restoring normal immune function. It is used to treat other autoimmune illnesses and showed promise in a pilot study with PANDAS patients.

“We predict that IVIG will have striking benefits for OCD and other psychiatric symptoms, and will prove most effective for children who show high levels of anti-brain antibodies when they enter the study,” said Swedo.

Prospective study participants are first screened by phone by investigators at the NIH or the Yale Child Study Center. Those who meet eligibility requirements are then randomized to receive either active IVIG or a placebo procedure during a brief inpatient stay at the NIH Clinical Center. The researchers remain blind to which children received the active medication; after 6 weeks of placebo control, they give any children whose symptoms fail to improve the option to receive open-label active treatment.

In addition to assaying for antibodies that attack brain cells, the researchers use magnetic resonance imaging to see if the treatment reduces inflammation in an area of the brain known as the basal ganglia, which is thought to be the target of the errant antibodies. They also analyze levels of immune system chemical messengers (cytokines) in cerebrospinal fluid and blood – with an eye to identifying biomarkers of disease activity and potential predictors of treatment response.

The study was launched with support from the NIH Clinical Center’s Bench to Bedside program, which encourages such intramural-extramural collaborations in translational science.

Reference:

Swedo, SE, Leckman JF, Rose, NR. From Research Subgroup to Clinical Syndrome: Modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Feb 2012, Pediatrics & Therapeutics.

Source:  National Institute of Mental Health

Update on Bizarre Outbreak of Tourette-like Symptoms in New York

Back in November, I noted that there was a bizarre outbreak of Tourette-like symptoms in  a number of high school girls in LeRoy, New York.  Since that time, the number of people affected has increased, and controversy has continued to swirl around that cause of the outbreak.  While some have argued that the cases are due to conversion disorder (“mass hysteria”),  others have sought a more organic basis.  Erin Brockovich has been conducting her own investigation into the possibility that environmental contaminants are responsible.  As of today, there is no evidence that environmental contaminants are the likely cause, but investigations are not complete.  Others have claimed that PANDAS  (now called PANS) is the cause (i.e., an autoimmune response to infection gone awry).  An article by Alison Motuk in Nature provides some of the background on this case and the possibilities that are being explored.   The following segment and other news clips linked at the end of the segment give a sense of how complicated this situation has been:

On a positive note, although the cause of the mystery is still unresolved, some of those affected are now getting better.

 

Join Me at an All-Day Workshop for Educators & Parents on December 5th

I’ll be conducting an all-day workshop for educators on Monday, December 5, 2011 at the Grappone Conference Center in Concord, New Hampshire. The event is sponsored by the University of New Hampshire Institute on Disability and is geared to regular and special education teachers, school psychologists and social workers, behavior specialists, occupational therapists, administrators, and parents.

Description:

Neurological disorders that emerge in childhood often have significant impact on students’ academic, behavioral, and social-emotional functioning. Participants will learn about the cardinal features of Tourette’s Syndrome, Obsessive-Compulsive Disorder, Attention Deficit Hyperactivity Disorder, Executive Dysfunction, Mood Disorders such as Depression and Bipolar Disorder, and the memory deficits, sensory issues and “storms” that sometimes accompany them. Strategies and assistive technology to accommodate symptom interference in activities such as handwriting, homework, math calculation, and written expression and big projects will be described. Pitfalls in behavioral interventions, and simple social skills and problem-solving interventions will also be identified.

For more information on the workshop and registration information, download the brochure or register online at www.iod.unh.edu.

Hope to see you there!

 

Obsessing Over Strep Throat in Kids

A site commenter kindly pointed me to an article about some research out of Tel Aviv University that has not yet been published, but it will be of interest to those interested in “PANDAS” or the strep connection to Obsessive-Compulsive Disorder (OCD):

… Prof. Daphna Joel and her team of researchers at Tel Aviv University’s Department of Psychology have now scientifically demonstrated that strep can lead to brain dysfunction and OCD. Dr. Joel says their breakthrough could lead to new drugs for treating OCD, and may in the future prevent the psychiatric disorder altogether.

Conducted by the PhD student Lior Brimberg and in collaboration with Prof. Madelaine W. Cunningham of the University of Oklahoma, the research, recently presented at the 13th Congress of the European Federation of Neurological Societies in Florence, Italy, is expected to be published by the beginning of next year.

[...]

Working with the world’s leading specialist in strep-related heart disease, Prof. Cunningham, the researchers developed a new animal model to show how exposure to strep affects the brain and leads to a number of physical and mental ailments.

In her Tel Aviv University laboratory, Prof. Joel and Brimberg created an animal model using rats exposed to the strep bacteria. Comparing them to a strep-free control group, Prof. Joel measured a distinct difference in behavior in the strep-exposed animals.

First, the strep-exposed rats developed a strep antibody which deposited in their brain, confirming the suspicions of previous researchers. Those exposed also developed balance and coordination difficulties, as well as compulsive behaviors such as increased and repetitive grooming.

More important, they also found that the strep antibody binds itself to dopamine D1 and D2 receptors in the brain. This finding is in harmony with the fact that one of the main drugs for treating Sydenham’s Chorea, a motor disorder associated with strep, targets these same dopamine D2 receptors.

“We were able to show that these antibodies are binding to receptors in the brain and changing the way certain neurotransmitters operate, leading to brain dysfunction and motor and behavioral symptoms,” Prof. Joel says.

Read the article on American Friends Tel Aviv University.

New research calls connection between strep infections and tics and obsessive-compulsive symptoms into question

PANDAS – a possible connection between strep infections and acute exacerbations or dramatic onset of tics or obsessive-compulsive symptoms – has been quite controversial since it first started being investigated in the early 1990′s.  Now a new study by Dr. James Leckman and his colleagues finds no evidence for PANDAS in children who meet established diagnostic criteria for PANDAS.

Here’s the abstract from their study, “Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study,”  which is published in the February, 2011 issue of the Journal of the American Academy of Child and Adolescent Psychiatry:

Objective
The objective of this blinded, prospective, longitudinal study was to determine whether new group A β hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or OC disorder without a PANDAS history served as the comparison (non-PANDAS) group.

Method
Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25-month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results.

Results
No group differences were observed in the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions of a total of 51 (12%), a newly diagnosed GABHS infection was followed, within 2 months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group.

Conclusions
This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria.

These findings, although not based on a large sample, will undoubtedly stimulate a lot of discussion among professionals. If 12% of new infections trigger an acute exacerbation of symptoms, how do we explain that? And can we predict which children will experience that problem? If the diagnostic criteria are not supported by the data, are there any diagnostic criteria that would be? And will children who experience the problem once experience it every time they have a strep infection?

I haven’t read the full study yet, but I look forward to reading it.

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