MIND ON THE RUN:
PANDAS: A Diagnostic Conundrum
By Kristi Wees, MSc Chemistry
Chief Patient Advocacy Officer
Pediatric Alliance — Arcadia
(Musical accompaniment: “Smoke Gets In Your Eyes” by The Platters)
“He who knows only one language, knows none”
— Johann Wolfgang von Goethe
The prerequisite for making the diagnosis of PANDAS (Pediatric Auto-immune Neuropsychiatric Disorder Associated with Streptococcal Infections) or PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) is having a high index of suspicion, which precludes an unconscious bias that the patient or the parents are inaccurate historians or unreliable narrators. This is true to an ever greater degree when the symptoms present in an individual with an underlying neurodevelopmental condition, such as autism or sensory integration disorder.
The primary requisite for suspicion is the sudden presentation — in whatever term it is labelled: “out of the blue,” thunderclap, overnight, foudroyant (French for “strike with lightning”). There may be very objective alterations in the patient’ behaviors: Motor or vocal tics never previously exhibited, extremely restrictive eating with documented weight loss, deterioration in handwriting (usually small and unintelligible). When the alterations in behavior are subjective, their documentation will be more nebulous, casting doubt and “smoke” in the eyes of the beholder: Obsessive-compulsive traits never before exhibited, perseveration with urination manifested as extraordinary frequency, subtle decline in cognitive abilities, profound anxiety (such as separation anxiety in older children). An elite athlete, for example, may refuse to go to the practices he or she once savored. Abrupt personality changes, such as temper tantrums, school refusal, or even psychotic ideation in an adolescent, will befuddle the most astute, seasoned psychologist.
In children with pre-existing deficits, such as those with autism, the key feature will be sudden deterioration in baseline behavior and capabilities — for example, the appearance of tics on a stable medication regimen or an overwhelming increase in self-injurious behaviors. After common, everyday triggers such as infection, constipation, and dental pain have been ruled out, an assessment for PANDAS/ PANS is warranted. Of course, the precise etiology can be difficult to tease out.
Although the time-honored throat culture is the gold standard for diagnosing acute streptococcal pharyngitis (“strep throat”), this test is of little or no utility in the identification of PANDAS. Since it takes at least two weeks for the host’s immune system to produce the autoantibodies that cross the blood-brain barrier and attack the relevant centers in the brain, the strep bacterium has long left the nasopharynx, the “scene of the crime.”
The documentation of PANDAS is predicated on the identification of the selective antibodies produced in response to the strep antigens that instrument the “molecular mimicry” discussed in our previous articles (read them here and here). Of these antibodies — anti-streptolysin O (ASO), anti-hyaluronidase, anti-streptokinase, and anti-deoxyribonucleases (DNases A,B,C, and D) — anti-DNase B is the most sensitive and most likely to be elevated in even the mildest throat or skin strep infection. Generally, a battery of these antibodies is examined — ASO titer, streptozyme (a collective test), and anti-DNase B — in order to identify a preceding strep infection with high fidelity.
Since other infectious triggers can produce the same clinical picture (PANS), bloodwork should include serology for those that can be reliably identified: Mycoplasma (the agent of “walking pneumonia”), Epstein-Barr virus (the cause of infectious mononucleosis), Borrelia burgdorferi (the trigger for Lyme disease). Other potential agents — chicken pox, influenza, herpes simplex — are evident by history and physical exam. We generally test for co-existent auto-immune diseases, such as lupus erythematosus, Hashimoto’s thyroiditis, and celiac disease. As with all laboratory studies, clinical correlation is paramount.
A major conundrum exists when the acute PANDAS symptoms are superimposed on those pre-existing in a child with an underlying neuro-developmental issue, for example, sudden worsening of anxiety or OCD behaviors in an individual with an autism spectrum disorder. In this scenario, the smoke can be blinding.
To be continued tomorrow…