PAS AND PANDAS. An increasingly frequent diagnosis.

Then you may know a child who has pediatric acute-onset neuropsychiatric syndrome (PANS) or pediatric autoimmune neuropsychiatric disorders associated with streptococcal disease (PANDAS). According to the American Academy of Pediatrics, it is estimated that at least 1 in 100 US schoolchildren have PANS, and that number is increasing every day.

More than half of all children with PANS will be misdiagnosed and mistreated for more than a year. Most children are misdiagnosed as having psychiatric illnesses, behavioral problems, or parental concerns.

PANS / PANDAS is a neuroinflammatory encephalitis modulated by the immune system, and without the appropriate antimicrobial, anti-inflammatory, and immunomodulatory treatments, the evolution is long and torpid.

Diagnosis:

PANS is a neuroinflammatory encephalitis that can have multiple triggering factors: infectious and non-infectious.

Many infections are possible triggers for PANS, including mycoplasma pneumonia, influenza, Epstein-Barr virus, Lyme and other tick-borne infections, HHV-6, HSV1 and 2, parvovirus B19, coxsackievirus, cytomegalovirus, and candida. Non-infectious triggers include environmental toxins such as mold, heavy metals, and other toxic exposures, as well as metabolic disorders such as diabetes and cerebral lupus.

Supplementary tests:

PANDAS patients have a history of recent or recurrent strep infection that does not necessarily present as pharyngitis. Cultures should be taken from the throat, nasal cavity, perianal/vaginal areas, and any impetiginized skin lesions. Blood tests often reveal persistently elevated antistreptolysin O (ASO) and anti-DNase B antistreptoplasty levels.

Quantitative IgG and IgM antibody levels should be assessed for other potential infectious triggers: these may include tests for mycoplasma pneumonia, influenza virus, Epstein-Barr virus, Lyme and other tick-borne infections, HHV-6, HSV1, and 2, parvovirus B19, coxsackievirus, cytomegalovirus, candida, and others, as indicated by the child’s history. It should be noted that the presence of very high IgG titers (concentration) may represent persistent chronic active infection despite negative IgM titers.

If all antibody levels are negative and no infection is detected, non-infectious triggers should be considered. Appropriate testing for mycotoxins, heavy metal exposures, and other chemical exposures should be performed.

The Cunningham panel, developed by immunologist Dr. Madeleine Cunningham who has been at the forefront of PANS research, tests for four neuronal autoantibodies (anti-dopamine D1 and D2L receptor, anti-lysoganglioside GM1, and anti-tubulin) as well as activity of the calcium-dependent protein kinase II (CaM kinase II) enzyme calmodulin that was found to have elevated activity in patients with PANS.

Treatment:

The “conventional” treatment for PANS incorporates:

psychiatric/behavioral interventions,
immunomodulatory therapies
antimicrobials to treat and prevent infection.
In relapses, there will be debilitating symptoms, OCD symptoms, tics, problems with memory and cognitive processing, severe impairment in writing, and emotional lability.

Psychiatric medications may be necessary in times of crisis for severe OCD, anxiety, depression, ADHD symptoms, sleep disorders, and other neuropsychiatric symptoms. However, these medications and behavioral interventions are merely Band-Aids and are often not as effective until neuroinflammation, infections, immune dysfunction, and other underlying causes are addressed.

Other treatments may include a trial of NSAIDs, a short three- and five-day burst of oral corticosteroids, pulse-long oral prednisone, or intravenous (IV) methylprednisolone/oral dexamethasone.

Antimicrobial treatment and prophylaxis are critical in the management of PANS and PANDAS. Conventional antibiotic regimens are more defined for the treatment of associated acute streptococcal infections in patients with PANDAS. The benefit of long-term antibiotic prophylaxis is less clear; however, most children appear to benefit from prophylactic antimicrobials to reduce the likelihood of a PANDAS outbreak after repeated strep exposure.

Other interventions may include supporting the gut microbiome and gut connection with probiotics and glutamine; reducing oxidative stress and inflammation with omega-3 essential fatty acids, antioxidants, curcumin, quercetin, and an anti-inflammatory diet; optimizing immune function and the Th17 response with specialized mediators such as fisetin (a bioactive flavonol) or Skullcap; optimize nutritional deficiencies and deficiencies; supports optimal methylation and detoxification with active vitamins B9 and B12 and liposomal glutathione; and addressing mitochondrial dysfunction with CoQ10.