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What is PANS/PANDAS and is it treatable?

The knowledge and awareness about Pediatric Autoimmune Neuropsychiatric Disorders Associated with Strep (PANDAS) is rapidly growing, but did you know that of the nearly 150 different strains of Group A streptococci (GAS) infections, only 10-12 are thought to account for symptoms of PANDAS? Researchers are continuing to learn more about the exposures to multiple infectious organisms and the relationship to innate immunobiological mechanisms and the potential for subsequent autoimmune and/or autoinflammatory processes.

What is PANDAS?

PANDAS symptoms can take on various forms, but a typical presentation often involves a sudden or abrupt onset of symptoms such as anxiety, emotional lability or depression, behavioral changes, poorer school performance, and sensory or motor disturbances. It’s thought that many children develop an immunity to GAS prior to puberty, which is why PANDAS is often said to be a pre-pubertal condition, though it’s not impossible for an infection to occur after puberty.

PANDAS was initially described as a post-infectious autoimmune process in the 1990’s as the first comprehensive report on children with obsessive-compulsive disorder (OCD) and tic disorders was comprised by Swedo, Leonard, Garvey, Mittleman, & Albert et al. (1998). Their study describes the connection between OCD and infection, namely Group-A beta hemolytic streptococcus (GABHS) infections, which included research by clinical investigation through the research program of the National Institute of Mental Health (NIMH) [1]. An example of a similar condition results from untreated GABHS that can lead to rheumatic fever and Sydenham chorea, a neurological presentation of rheumatic fever [2]. The autoimmune etiology for PANDAS is thought to be similar to that of Sydenham’s chorea (SC), known as a manifestation of rheumatic fever which is precipitated by streptococcal infection [1]. In SC, antibodies have been identified that cross-react against neuronal lysoganglioside and streptococcal N-acetyl-beta-D-glucosamine [3].

Understanding SC has provided conceptualization and framework for PANDAS as they have immunological similarities. In PANDAS, when a streptococcal infection triggers an autoimmune response, the host antibodies directed against the Streptococcus pyogenes cross-react with human proteins [5]. In other words, antibodies mistakenly attack brain tissue which increases inflammation, namely in the basal ganglia, which can induce the sudden onset of movement disorder and neurological behaviors [1]. To date, abnormalities of the cortico-basal ganglia circuitry are correlated with OCD and tic disorders and are important to understand the pathophysiology as it pertains to PANDAS. Additionally, functional imaging studies in those with OCD have displayed abnormal metabolic activity in the orbitofrontal cortex and the anterior cingulate/caudal medial prefrontal cortex [6]. The cortico-basal ganglia network is sometimes referred to as the “OCD circuit” as the activity here has been notably increased in those with OCD compared to controls, as well as significantly decreased following successful treatment [7].

In addition to OCD, many psychiatric comorbidities have been identified to be associated with PANDAS including attention-deficit/hyperactivity disorder (ADHD), mood disorders, separation anxiety, food restriction, vocal and motor tics, and frequent urination. The onset of these symptoms can be abrupt, and distinctly contrast children’s behavior prior to the onset of symptoms, which can cause significant stress on both child and their families [8]. The average age of onset is between 4 and 7 years old. If children with PANDAS are exposed to streptococcal infections, this can cause a “flare” in symptoms, often occurring throughout the school year or in the presence of other children, as well as if the child’s family members are carriers of streptococcal infection [1].

What is PANS?

According to the NIMH, Pediatric Acute-onset Neuropsychiatric Syndromes (PANS) is a broader categorization when a specific infectious trigger isn’t identified and similar symptoms can be triggered by more than one infection, including varicella, Lyme borreliosis, and mycoplasma [9]. PANS typically emphasizes clinical symptoms rather than specific etiology. It’s important to understand the pathophysiology of both PANS and PANDAS, however, to better understand the implications that different infections have on the brain and the subsequent symptoms, similar to the way that understanding SC provided a framework for understanding PANDAS, as well as for PANS as the prevalence of such conditions is rising [10].

Treatment Options

  • Treatment for PANDAS often includes the use of antibiotics to treat the GAS infection and in some cases, tonsillectomies are indicated.
  • Immunomodulatory therapy, such as IVIG, has been used as a potential treatment for PANDAS, as well as plasmapheresis. IVIG is a therapy intended to support those with a weakened immune system by providing the body with antibodies necessary to fight infections. Plasmapheresis is the process by which harmful auto-antibodies are taken from the bloodstream more directly, and the blood is essentially “cleaned,” and then returned to the patient.
  • While there aren’t definitive guidelines for treating PANDAS, many children and families resort to more integrative and holistic modalities to support whole-body wellness and restoration.

Immune Support is a Must

  • Prioritize diet and nutrition: This is imperative to optimize gut function and restore microbial diversity within the gut as it comprises 70-80% of the immune system and neurotransmitter function. It’s extremely important to seal the gut lining to prevent the bidirectional connection to the brain from becoming leaky and permeable to different proteins and pathogens.
  • Consult with your provider about addition modalities to address underlying infections such as homeopathy, herbs, supplementation, or Low Dose Immunotherapy.

It’s important to remember that it is possible for PANDAS children to make significant improvement and in some cases, recover fully, so remain hopeful! If you have questions about PANDAS, come to our monthly Autism, ADHD, PANS, PANDAS Q&A Group with Stephanie Beseth!

Resources

  1. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases
  2. Tonsillectomies and adenoidectomies do not prevent the onset of pediatric autoimmune neuropsychiatric disorder associated with group A streptococcus
  3. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea
  4. Antibody-mediated neuronal cell signaling in behavior and movement disorders
  5. From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome)
  6. Toward a Neurobiology of Obsessive-Compulsive Disorder
  7. Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder
  8. Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood Obsessive-Compulsive Disorder
  9. Anti-basal ganglia antibodies: a possible diagnostic utility in idiopathic movement disorders?
  10. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)
  11. PANDAS Network: What is PANDAS