Sudden and Severe Onset OCD (PANS/PANDAS)– Practical Advice for Practitioners and Parents

Compiled by Michael Jenike MD and Susan Boaz mom and advocate

Other PANS/PANDAS Information
PANS/PANDAS Information Talking to Your Pediatrician about PANDAS/PANDAS to Pans (PDF)Microbes and Mental Illness (blog)Participate in our PANS/PANDAS Awareness Campaign SurveyRelevant Research What every Psychiatrist should know about PANDAS

Many thanks to the contributing clinicians and researchers who answered our questions with great patience and whose love for these children is not always listed on their CV but is always their most obvious qualification Dan Geller MD Tanya Murphy MD Eric Storch PhD Kyle Williams MD Jim Leckman MD Madeleine Cunningham MD Karen Newell PhD and Sue Swedo MD And to the moms and dads who have dedicated their lives to raising awareness about this disorder – you are the silent heroes to countless children.

“My child was fine last week last month – and now I have lost her This is not my child; what has happened??? What do I do??”

For every parent of a child with an illness especially a mental illness there is a particular story But when you meet a parent of a child with PANDAS (typically a child between ages 3-14) you will hear the same panicked story over and over A child who was happy at home and at school and was social and athletic is now walking in circles for hours washing hands until they bleed asking the same questions over and over – and over A child that used to be comforted by a hug is now inconsolable They may be begging parents for help begging for a way tond the horror that exists only in their minds Imagine a child screaming in terror in a corner and a parent unable to hold them These parents will tell you in detail about the day or week that their child changed Here is what life looks like now – children may exhibit some or all of these symptoms:

Acute sudden onset of OCD Challenges with eating and at the extreme end anorexia Sensory issues such as sensitivity to clothes sound and light Handwriting noticeably deteriorates Urinary frequency or bedwetting Small motor skills deteriorate – a craft project from yesterday is now impossible to complete (see images below) Tics Inattentive distractible unable to focus and has difficulties with memory Overnight onset of anxiety or panic attacks over things that were no big deal a few days ago such as thunderstorms or bugs Suddenly unable to separate from their caregiver or to sleep alone Screaming for hours on end Fear of germs and other more traditional-looking OCD symptoms

You will often find these parents on the computer every night desperate for an explanation that makes sense They are seeking specialists who can help – and finding no answers They are starting to feel crazy themselves because no one seems to believe what they are going through.

If you are a pediatrician or pediatric therapist faced with this family in your office this may look daunting However let’s take a minute to walk through options that are available to parents medical and mental health professionals and kids suffering from this disorder These treatment recommendations were developed from interviewing clinicians and researchers around the country so that you can potentially stop the disease in its tracks while you referring these children for additional help if needed

PANDAS Drawings

Panel A– Drawing produced during an acute exacerbation of OCD and other symptoms of PANDAS which appears quite messy and immature.

Panel B – Age-appropriate picture drawn after treatment with IVIG and symptomatic improvement.

Drawings that demonstrate loss of fine motor skills during acute illness

Handwritng samples documenting dysgraphia during acute illness.

Images courtesy Swedo SE Leckman JF Rose NR (2012) From Research Subgroup to Clinical Syndrome Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) Pediatr Therapeut 2:113 doi:10.4172/2161-0665.1000113

What is Pediatric Autoimmune Neuropsychiatric Disorder Associated with Strep or PANDAS?
PANDAS was defined in 1998 by Dr Sue Swedo Over the prior decade Dr Swedo had been studying Sydenham Chorea where 70% of patients exhibit sudden onset OCD symptoms before or after this classic movement disorder She and other researchers were finding children who had sudden onset OCD symptoms without the carditis (heart inflammation) or movement disorder normally characteristic of Sydenham Chorea and acute rheumatic fever

Auto-antibodies have been implicated in the carditis of Acute Rheumatic Fever and Dr Swedo theorized that perhaps a related set of antibodies were mistakenly attacking the basal ganglia (part of the brain) rather than the intended streptococcal bacteria triggering the movement disorder/sudden onset of OCD In July 2010 researchers met at the NIH to discuss the past decade of clinical findings Of significance the panel found that while strep throat seems to be a trigger it may not be the only trigger Sudden onset OCD could be triggered by other diseases including Lyme Mono Mycoplasma and the flu virus (such as H1N1) Based on this and other clinical reports the panel modified the research definition of PANDAS.

How to Identify a PANDAS Child

Sudden dramatic onset is the most salient characteristic and differentiates PANDAS from a more frequent pediatric OCD presentation – which involves subclinical symptoms becoming gradually more severe Incapacitating fears and anxieties seem to come on “overnight” with many parents being able to name the exact day when their child changed In addition while the mean age of OCD in children is between 9 and 10 years of age PANDAS cases can start at a younger age such as 5 or 6 often corresponding with a diagnosis of strep

Physicians are encouraged to assess for:

A history of sore throat fever exudative pharyngitis cervical adenopathy (enlarged and tender lymph nodes in the neck) enlarged or damaged tonsils Atypical presentations of strep especially in young children include abdominal pain and vomiting vaginal or perianal redness In some cases of PANDAS the strep appeared to be “hiding” in the sinuses or middle ear resulting in a negative throat culture It is also possible that non-strep organisms can cause a similar neuropsychiatric illness in vulnerable children Therefore it is important to check for mycoplasma mono or exposure to Lyme disease

During the meeting at NIH last year researchers and clinicians across the country began to revise the criteria defining this illness in children Based on that conference because there are non-strep causes of sudden onset illness researchers changed the name of the disease to PANS Pediatric Acute-Onset Neuropsychiatric Syndrome

Mental and medical professionals should look for

Abrupt dramatic onset of OCD is the first diagnostic criterion for PANS For those familiar with the CYBOCS (Childhood Yale Brown Obsessive Compulsive Scale) scores some clinicians look for an increase in total score of more than 16 in the course of a few days Children may have mild “quirks” orven some signs of OCD prior to this abrupt dramatic onset In retrospect some clinicians suggest that mild micro-episodes mayven have occurred in the past However in the space of a few days they “fall off a cliff” dramatically causing a significant decrease in the child’s ability to function Impairment is significant Parents can usually name the day that the crisis occurred and have vivid memories of the first obsessions or compulsions because of their extreme nature As an example a normally joyful balanced emotionally independent social child may turn into a child that has extreme temper tantrums that are out of character and can no longer leave a parent’s side without accommodation Panic attacks and unusual anxieties are not uncommon In addition to the typical obsessional fears and compulsive behaviors this criterion also may be satisfied by the sudden severe onset of food avoidance anorexia and eating restrictions Clinically these occur as solitary symptoms among PANS patients as well as from complications resulting from obsessional fears of choking vomiting or of contaminated foods Although there appears to be uniformity in the acuity and severity of onset of the co-occurring symptoms there is great variability in the nature of the symptoms accompanying the OCD As a result the second major criterion for PANS is the concurrent acute onset of additional symptoms from at least two of the following seven categories

anxiety (particularly acute separation anxiety and irrational fears) emotional lability and/or depression irritability aggression and/or oppositional behaviors behavioral (developmental) regression sudden deterioration in school performance sensory or motor abnormalities (particularly dysgraphia/ trouble with handwriting) somatic/physical signs and symptoms

As in most of psychiatry PANS is a clinical diagnosis meaning that there are currently no laboratory or genetic tests that can confirm the diagnosis As such a second opinion to find consensus on the diagnosis of PANS between two experienced physicians may be useful.

Additional Medical Testing to Consider Prior to Onset of Treatment

Many physicians report that a throat culture appears to be key (even if there are no signs or symptoms of pharyngitis) Due to the difficulty in properly sampling these children a two-swab sample should be taken to check for bacterial colonization The first swab should be a rapid strep test It is very important that the culture is obtained properly by vigorously swabbing across the entire pharynx behind both tonsils and the uvula If the child doesn’t gag and protest the swab is probably inadequate If negative use the second swab for a 4-hour agar plate culture If these are both negative consider testing for Lyme disease Mycoplasma vitamin D Ferritin and thyroid Many children with recurrent upper respiratory infections have immune deficiencies and would benefit from an immune function assessment such as blood counts measuring quantitative immunoglobulins and a referral to a pediatric immunologist

Finally many physicians rely on antibodies to the exotoxins of streptococcus to confirm a prior infection measuring ASO and AntiDNaseB These tests have fixed windows where the measurement may begin to be positive 1-8 weeks after initial infection Typically two measurements are required The first should be obtained as soon as possible after the suspected infection and the second at least six weeks later It is currently unknown whether carrying the bacteria without an active infection alone is sufficient to cause symptoms in PANS children.

If test results are all normal it does not rule out a diagnosis of PANS and exposure to infections from close contacts should be considered

Treatment Options and Strategies to Consider for PANS

While acknowledging the need for additional research we also cannot sit idly by while children scream in terror We have to help children suffering today Clinicians around the country have started treating our kids Best practices suggest that one develop a treatment plan based on interventions with the minimum effective dose an intervention with the best cost/benefit ratio (less intrusive minimal short term and long term side effects good at preventing relapse easy to administer tolerated well) and treatments that have the most research behind them Research can include controlled studies (better) and case reports (good but less informative) We will rate each of the following treatments currently being used as a guide for professionals and parents to consider when trying to determine the best course of action This is said with the caveat that at this point in time PANDAS and PANS treatments are drastically under researched Please see the end of this article for more about how to help on this front.

IVIG The original research studies investigating possible treatment options were done by giving children IVIG (intravenous immunoglobin) Essentially this treatment gives a child antibodies from a myriad of donors We don’t know exactly how IVIG works but it appears to help in a number of autoimmune illnesses

In PANDAS IVIG reduced the OCD symptom severity for 82% of children suspected of having PANDAS in a small study that is now being repeated at the NIH IVIG is offered to children in a clinical environment – but is often not covered by insurance and is expensive While IVIG is usually considered quite safe for treating auto-immune disorders there are several risks Nausea vomiting and headache are not uncommon and in rare instances aseptic meningitis or allergic reactions may occur Although most side effects are not harmful in the long term they are unpleasant and therefore IVIG therapy is generally recommended only for severe or persistent cases or as indicated for immune deficiency disorders

Antibiotics Dr Swedo also did research showing that using antibiotics as a prophylaxis to prevent strep successfully reduces neuropsychiatric exacerbations Another study will start soon as a collaboration between Harvard and the University of South Florida They will be examining a common treatment course successfully used by clinicians using antibiotics in children with PANDAS Early in the disease if strep is present this is an obvious course But no research has yet been done on why many clinicians find that a longer term course of antibiotics often seems to offer great hope to families suffering from this disease –even after the actual triggering illness is over As such some physicians have found the following particularly helpful for new sudden onset cases

Use antibiotics for 3-6 weeks initially Use of augmentin has anecdotally been found to be more effective at a relatively high dose as well as the cephalosporins (cephalexin cefdinir) and azithromycin Consider using probiotics but not at same time of the day; allow 2-3 hour window between If no improvement is seen after 3-4 weeks a physician may consider an alternate class of antibiotic treatment If symptoms completely remit a trial off the antibiotic may be attempted If symptoms return additional treatment may be warranted

However in many cases a physician will see a child a several weeks after the initial onset or in a second exacerbation In that case some clinicians have recommended the following

A throat culture can still be very informative at this point as well as antibody levels Then treat with antibiotics as above while waiting for the results If there is a marked reduction in symptoms gradually wean With a recurrence antibiotics are reintroduced and continued as needed Try to gather retrospective information ask for detailed pediatrician records to be forwarded and nail down thexact timing of testing and labs Since prior testing may have been limited a trial of antibiotics appears to be low risk

Exposure and Response Prevention (an intervention under the broader umbrella “Cognitive Behavior Therapy or CBT) Unlike traditional onset OCD where research clearly guides a mental health and medical professional’s decision making about how to proceed with treatment PANS onset OCD is still under researched As we wait for studies to be completed we still need to develop treatment strategies that can address the pain and suffering of children and families now For many PANS children the suddenness of onset and the migratory nature of the obsessions/compulsions can make Exposure and Response Prevention therapy or ERP challenging; however a combination of a medical intervention and traditional ERP might be the best course of action at this point in time For some children an initial treatment with antibiotics or IVIG results in significant relief of symptoms For those with slow or partial remission of symptoms ensuring that ERP is included seems to be critical Children develop habits and fears quickly and they may use ERP treatment to teach their brain to ignore the irrational fear signals they have been receiving ERP teaches a child concrete tools to overcome OCD thoughts on a daily basis Many clinicians find that learning ERP allows the entire family to function more calmly during future exacerbations while seeking medical help Some recent but preliminary work by a group at University of South Florida found strong effects for this approach in children with PANDAS (Drs Storch & Murphy)

SSRIs Most clinician experienced in treating children with PANDAS do not initially recommend SSRI especially given the very young age of many of the children However as the disease course continues they may find relief with the use of SSRIs in much lower doses than is normally recommended for children with OCD Close monitoring is strongly recommended as very young children may have more adverse behavioral or neurological effects Occasionally mood stabilizers have been reported as helpful as the presence of mood volatility in PANS/PANDAS is a major limitation in the use of SSRIs Please see this link for more information about SSRIs

Plasmapherisis Dr Swedos’ original study included both IVIG and plasmapherisis. Plasmapherisis was the more immediate and effective option in the original study However as the most expensive and invasive treatment option this is rarely used in a clinical setting and is beyond the scope of this article For more information see the original research study or read more about plasmapherisis online.

Steroids As with all autoimmune diseases doctors have found that anti-inflammatory medications (such as corticosteroids) can beffective in both short and long term use However these can be very damaging to children in long-term use and should only be considered in careful consultation Some parents or clinicians have found that short-term use of steroids can help auto-immune triggered OCD once the initial infection is cleared Behavioral sideffects are sometimes seen in steroid therapies (especially mood symptoms) and can overlap with PANS symptoms Should additional research studies come available IOCDF will publish those findings

Ibuprofen and NSAIDs Some parents have reported that non-steroid anti-inflammatories (such as Ibuprofen) do seem to help symptoms This has led some researchers to consider that perhaps it is the anti-inflammatoryffects of the antibiotics IVIG and steroids on the blood-brain barrier that is resulting in improved symptoms While long-term use of NSAIDs carries its own issues some pediatricians prescribe a low-dose NSAID during significantpisodes Please consult with your doctor as there are multiple other issues to consider when using this approach

Summary Conclusions and Going Forward

As noted previously in the absence of research we cannot recommend doing nothing for these children Their suffering is intense And the risk of long-term damage cannot be ignored We also do not know if some of these children remit spontaneously later in adolescence We do not know if some of them grow into adults with the most treatment resistant OCD due to permanent basal ganglia damage While we research those questions offering treatment options at the local levelspecially in the first few months after onset could be critical to the long term success for these kids One prospective study conducted in a pediatrician’s office suggests that first-onset PANDAS symptoms may remit following successful treatment of the strep infection with antibiotics Unfortunately there has not been a follow-up report on these children so it is unknown if some childrenxperience a secondxacerbation following successful treatment of the initial onset of PANDAS symptoms.

Like Sydenham Chorea PANS provides a window into a whole new way of treating mental illness as a faulty immune response There are many researchers across the nation who have developed hypotheses about the cause contributing factors and treatment They need funding to move forward with this seed research before developing larger grant proposals If you are interested in learning more or in contributing towards this research the IOCDF welcomes your call or donation Dr Madeleine Cunningham often ends her presentations on PANDAS with this compelling quote “If auto-antibodies are proven to play a role in mental disorders then it will change the way mental illness is diagnosed and treated forever.” Being a part of this change – whether you are a treating physician a researcher a parent or a donor – might change your life forever too.