This blog is a way of sharing the information and resources that have helped me to recover my son Roo from an Autism Spectrum Disorder. What I have learned is to view our symptoms as the results of underlying biological cause, which can be identified and healed. I say "our symptoms" because I also have a neuro-immune disorder called Myalgic Encephalomyelitis.

And, of course, I am not a doctor (although I have been known to impersonate one while doing imaginative play with my son)- this is just our story and information that has been helpful or interesting to us. I hope it is helpful and interesting to you!

Tuesday, January 13, 2015

Dr Susan Swedo presenting at the 2014 West Coast PANDAS Symposium

The video for this presentation can be viewed here.  Dr Swedo is the chief of Pediatric and Developmental Neuroscience at the NIMH.

A little background about OCD and PANDAS

It was in the 1980s that emphasis shifted from seeing OCD as something caused by bad mothering, to something more biological.  Dr Swedo says that OCD is the ultimate brain disorder, in which there is a well established network with dysfunction at many levels.  In adult patients who have significant depression and anxiety, the dysfunction is mainly in the orbital frontal cortex.  In children who have the triad of OCD, tics and ADHD, the dysfunction is mainly in the basal ganglia (also sometimes called the striatum, because that is what it is called in rats).  As for the locus of action for the antibodies in PANDAS, if the child has mostly tics, it is the putamen that is more affected.  If the child has primarily OCD, it's the caudate nucleus, and the ADHD/impulsivity is when the globus pallidus is more affected.

Dr Swedo's research into post-infectious OCD was first published in 1994 under the term PITAND which stood for Pediatric Infection Triggered Autoimmune Neuropsychiatric Syndrome.  The first cases they found were triggered by chicken pox, influenza, and strep.  They chose to focus on the strep cases because there was already a body of knowledge about Sydenham's Chorea that could be used, and because it seemed like a more simple and straightforward focus than the other triggers.

The "big picture" of PANDAS

At this point she takes a moment out of the presentation to share a "big picture" paradigm shift that she has had involving what PANS and PANDAS are and how they are related.  She says that you can imagine a large circle in the air, that encompasses the symptomatology of PANS/PANDAS.  This is not about cause at all, but about presentation.  If you imagine another circle in the air, that represents autoimmune encephalitis (of which PANDAS is one example), where those two circles intersect is PANDAS.  PANDAS is when the symptoms of PANS are caused by an autoimmune encephalitis following strep infection.

Most of the controversy surrounding PANS/PANDAS has to do with the "associated with strep" part.  Also, there was a printing error when the original work was published that left out the part about "sudden and acute onset", and the incorrect text has been used by detractors.

The basic model of true PANDAS can be taken from Sydenham's Chorea, in which certain strains of strep cause a genetically predisposed host to have a misdirected autoimmune response (by means of molecular mimicry) which attacks the basal ganglia in the brain and leads to the neuropsychiatric symptoms.  Much of the lecture is spent on elucidating the parts of this model.

The evidence for strep involvement

There are 5 reasons why they think that strep is involved. The first is clinical evidence and epidemiological studies (this is also the only evidence that exists to tie strep to both Sydenham's Chorea and Rheumatic Fever).  She discusses several studies that observed large numbers of school aged kids and their behavior, and correlated that with the presence of strep.  The second piece of evidence is that treatment of strep reduces the OCD and other symptoms.  The third is that prophylactic prevention of strep infection with antibiotics also prevents relapse of the OCD and other symptoms.  She presents several studies that support these claims.  The last two pieces evidence are that correlation between the autoantibodies and the OCD/tics has been demonstrated in humans as well as in animal models.

What does "susceptible host" mean?  

Kids with PANDAS come from families with OCD and tics.  20% of first-degree relatives (siblings and parents) of a child with PANDAS have OCD or tics.   Also, there was an increased level of Rheumatic Fever in the grandparents generation, and increased rates of autoimmune disorders among the parents' generation.  Despite the research into genetics, there is currently no genetic test that can tell whether a child will develop PANDAS or not.  A thorough family history is more effective.

The misdirected immune response

It appears that PANDAS is a "forme fruste" of Sydenham's Chorea, meaning a not fully developed form.  In SC the neuropsychiatric symptoms begin several weeks before the choreiform movements, indicating that the threshold for this immune response to trigger the neuropsychiatric symptoms is lower than that for the movement disorder symptoms.  There is a striking difference in executive function deficits among the kids with PANDAS and SC vs kids with "standard" Tourette's and ADHD.  She also discusses research at this point (around 25 or 26 minutes in) showing the autoantibodies present in PANDAS and SC, but not in "garden variety" OCD or tic disorders.  She also presents research showing that the antibodies are signally the cell and leading to bioactivity, meeting the criteria needed to show that a disorder is an autoimmune encephalitis.  There is also research in animal models that shows the development of PANDAS-like symptoms from transferring the autoantibodes into previously healthy mice.

Autoantibodies and the basal ganglia

Around 30 minutes in, she discusses research into treatment methods, which provide supporting evidence for the role of autoantibodies in this disorder.  IVIG in PANDAS cases showed a 65% rate of improvement, whereas IVIG on non-PANDAS OCD cases didn't show any improvement.  This demonstrates both that PANDAS OCD is not the same as all OCD, and also that improvement from IVIG is not simply a placebo effect.  There is at least one study showing changes in the brain via imaging before and after the IVIG treatment.  Research also suggests that plasmaphersis is more effective than IVIG.

She reiterates that PANDAS is post-streptococcal autoimmune encephalitis.  It has an acute onset following Group A Strep infection, there is evidence of cross-reactive antibodies against neuronal cells of the basal ganglia, there is improvement with immunomodulatry therapy, future episodes can be prevented with prophylactic antibiotic therapy, and animal models exist.  These are the 5 criteria needed to show that something is an autoimmune encephalitis.

What about kids who don't have strep?  The PANS kids?

PANS is sometimes referred to as CANS, with the C standing for "childhood".  PANS can be caused by other microbes, such as mycoplasma and Lyme, as well as environmental factors and metabolic disorders.  The description of PANS symptomatology is a little different, with more recognition of eating disorder presentations.  She still emphasize the acute onset in PANS, like being struck by  lightning.  Severe self-restriction of eating is an issue for at least 1 in 5 children with PANS.  In PANS the child MUST have either OCD or an eating disorder, even though this means missing some kids who have predominantly tic-based issues.  The diagnostic criteria for PANS is presented on a slide at around 36 minutes into the talk.  She emphasizes that while diagnosis requires that kids have two of the seven additional criteria, nearly all of the kids have at least 5 or more of the symptoms from the list, making PANS a very recognizable disorder.

Eating disorders in PANS

These are of two types.  There is both the more classic anorexia nervosa disorder, driven by body distortions and fear of being overweight, as well as a form that is more driven by OCD that is characterized by fears of contamination (poison, microbes, unhealthy components), fear of choking or vomiting, or a sense of not deserving the food.  If the weight loss exceeds 10-15% of body weight body distortions become more prevalent.  She recommends that kids with eating problems get a swallowing study which may lead to treatment options.

Comorbid symptoms in PANS

80% of the kids have sleep disorders.  They originally suspected this to be due to anxiety, but now see it as the result of disruptions in the sleep cycle.  Research has been done showing that at baseline, a number of kids had a REM sleep disorder (failure to lose muscle tone and become paralyzed during REM sleep), which results in the child moving around a lot and thrashing around in their sleep (I think this would also include night terrors?).  Those kids need a sleep study.  Behavioral regression is common, especially separation anxiety that is seen in 98% of the kids.  This may also present as crawling, baby talk, and tantrums.  90% have difficulty with concentration.  Hyperactivity, inattentiveness, aggressiveness, and learning difficulties are also present in more than half of the kids.
One of the most clear signs she says is sudden onset of urinary frequency, urine accidents during the day or bedwetting at night, that is PANS.  This is a "hard" neurological symptom and does not occur with conversion disorder or as a psychiatric sequelae.  Deterioration of handwriting is common during a PANS episode, even if the child was only exposed to the pathogen and didn't become sick themselves.  At around 40 minutes in there are examples of changes of handwriting and drawing.

At 40:50 is information about doing a medical workup for suspected PANS.  This includes looking for occult infections (adenoids and tonsils, sinuses, urethra, anus).  Peri-anal strep is especially hard to find and treat.  Look for choreiform movements (examples of choreiform movements can be seen herehere and here.  Notice that the intensity can vary tremendously).  Testing for strep must be done correctly and carefully.  Rapid strep tests are often not positive. Throat swabs must be done thoroughly, not just a tickle of the throat.  Tests for ASO titers and Anti-DNAse only pick up about two-thirds of cases.  Only a rising titer indicates infection, so you need a baseline for comparison.

About 56% of patients seen at NIH for PANDAS are positive for the ANA test.  It generally indicates the presence of an autoimmune disorder, but keep in mind that around 10% of healthy children will have a positive ANA.  Tests through Moleculera lab (including cross reactive titers and CAM II Kinase activity) take 6 weeks to get back, so only helpful in long-term cases but not initial evaluation.   Swallow studies should be done on kids with eating problems, and sleep studies on kids with sleep disturbances.  A sleep study can also include an EEG.   If spikes and waves or slowing are found, this is considered by neurologists to be a sign of autoimmune encephalopathy (about 10% of PANS patients have these results).  She says that high-dose benzodiazepines can be helpful for kids with REM sleep disorder.  She also suggests a lumbar puncture to rule out other causes of the behavioral symptoms, such as encephalitis and meningitis.

Management of PANDAS/PANS

Eradicate the infection with at least 3-4 weeks of antibiotics (this is for new infections I think).  Cefdinar has shown good results.  Augmentin has dopaminergic and glutaminergic effects from the clavulinic acid component, they are working on a way to give only that piece.  Consider immunomodulatory therapy for a child who is mild to moderately ill, start with antibiotics, then move to steroids if that is not enough.  For kids whose illness is more severe and has them struggling to be able to leave the house, IVIG is a good place to start, but do the workup described above first.  Plasmapheresis should be considered in severe and life-threatening situations.  Life-threatening may include children who have stopped eating or lost too much weight, who are suicidal (especially if impulsive), and who go into rages that make them dangerous to themselves and others.

In helping the child recover she suggests Cognitive Behavior Therapy, including exposure with response prevention (this may not be tolerated during the acute illness).  Psychotropic meds may also be helpful.  Remember to start low and go slow with meds!  These may include SSRIs, tranquilizers and antipsychotics, anxiolytics (possibly benzos?), melatonin or stronger sleep aids, and possibly stimulant meds.  This will also include antibiotic prophylaxis to avoid additional strep infections.  Many people say that SSRIs are poorly tolerated in this group.  She says this is specific to the activating ones, but that there are other SSRIs that don't have those side effects that can be used.  By starting low she means to start with one tenth of the normal dose that would be given to a child.  20% of kids with PANS will have hallucinations and meet criteria for psychosis.