PANDAS/PANS and Autism

PANDAS and PANS
FacebookTwitter

Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal Infections, or PANDAS, is a common autoimmune disorder with far-reaching movement, behavioral, and cognitive consequences. Although we focus on the pediatric population by definition with PANS and PANDAS, immune-mediated OCD/Tics/Neuropsychiatric Disorders can also affect adolescent and adult populations and should always be considered when specific signs and symptoms emerge. Both PANS and PANDAS are clinical diagnoses differentiated by the abrupt onset of symptoms as listed below.

As noted by Dr. Sue Swedo at the NIH in the late 1990’s, PANDAS involves antibodies from a streptococcal infection reacting with brain tissue (specifically the basal ganglia), triggering movement and behavioral problems. Rheumatic Fever is an older known disorder that illustrates this same disease process, in which antibodies from a streptococcal infection attack the heart valves, joints, and brain and result in heart disease, arthritis, and Sydenham’s Chorea. Although bacteria set the vicious cycle in motion, the real damage in this type of autoimmune disorder stems from the antibodies and the inappropriate immune response.

In 2012, the triggers for an abrupt onset of neuropsychiatric symptoms were expanded to include other infections such as Mycoplasma and viruses as well as metabolic disorders including exposure to pesticides or anesthesia. As such, in addition to PANDAS, we now utilize the acronym PANS, Pediatric Acute-Onset Neuropsychiatric Syndrome.

Diagnostic Criteria for PANDAS and PANS

  • Abrupt, dramatic onset or recurrence of OCD
  • Acute-onset anorexia and/or severe, restrictive eating disorder
  • Concurrent presence of two of the following neuropsychiatric symptoms with severe and acute onset:
    • Separation Anxiety
    • Emotional lability
    • Behavioral/developmental regression
    • Sensory/motor abnormalities – handwriting deterioration
    • Deterioration of school performance
    • Urinary symptoms (urgency, frequency, enuresis)
    • Sleep disturbance (difficulty falling asleep, REM disinhibition/restless sleep)

Additional Signs and Symptoms of PANDAS and PANS

There can be many signs, symptoms, and comorbid diagnoses noted in children with PANS/PANDAS including irritability, personality changes, aggression, uncontrolled agitation, fear about bedtime regimen, fidgetiness, emotional lability, motoric symptoms (tics, motoric hyperactivity, compulsive rituals), sensory defensiveness, impulsivity, depression, dysthymia, ADD, and ADHD in addition to those presented in the graphic below.

Clinical Observations in PANDAS/PANS

Testing for PANDAS and PANS

Always keep in mind that PANS and PANDAS are clinical diagnoses.  Laboratory tools are limited and the traditional abnormalities of increased blood strep titers (ASO and DNAseB antibodies) and a positive throat culture are not always present. Therefore, normal levels of strep antibodies and negative cultures do not exclude the PANDAS diagnosis. Similarly, normal mycoplasma, viral or other titers do not rule out the diagnosis of PANS.

In atypical presentations, CaM kinase and anti-neuronal antibody testing can help to differentiate children with evidence of autoimmune encephalitis from those with tics, OCD, ADHD from other causes.  The most commonly abnormal parameters (in > 56%) are immune markers such as ANA.  Measuring other items such as zinc, magnesium, vitamin D and A and mitochondrial and thyroid markers may also be helpful in supporting appropriate treatments.

Treatment Options for PANDAS and PANS

The treatment of children with PANS and PANDAS is three-fold including antibiotics/antimicrobials, comprehensive immune therapy, and treatment of symptoms.

1. Antibiotics and Antimicrobials

  • Antibiotics
    • Used daily for treatment; important to also consider prophylaxis to prevent further reinfection.
    • Penicillin, Amoxicillin-Clavulanate, Azithromycin, Clarithromycin, Cephalexin, Cefadroxil, Cefdinir, Clindamycin, etc.
  • Natural Antimicrobial Therapies
    • Probiotics and Prebiotics including Saccharomyces Boulardii
    • Xylitol and BlisK12 to treat germs in the mouth and nose
    • Many herbs can help treat multiple germs:
      • Antimicrobial herbs for strep including:
        • Usnea
        • Taiga (Pine needle extract)
        • Berberine (Goldenseal)
        • Neem
        • Oregano Oil
        • Cordyceps
      • Antimicrobials herbs for mycoplasma:
        • Berberine/Goldenseal
        • Thyme/Oregano
        • Colloidal Silver (also effective for strep)
        • Houttuynia
      • Antimicrobials to consider for viruses:
        • L-Lysine
        • Monolaurin
        • Elderberry
        • Olive Leaf
        • Glycyrrhiza (Licorice)
        • Lemon Balm

2. Immune Modulation Therapy

  • Corticosteroids
    • Short-term use of tapering dose
    • Positive response often indicates the patient is more likely to respond positively to IVIG, but no response does not mean IVIG will be ineffective
  • Intravenous immunoglobulin (IVIG)
    • Derived from human blood; pooled from many donors
    • Can provide antibodies in those who are lacking them
    • Can help to inactivate antigens and slow down an overactive immune system that is functioning inappropriately
  • Plasmaphoresis
    • A type of plasma transfusion to remove antibodies
  • Intuximab
    • Monoclonal antibody (off-label for lupus, MS, CIDP)
  • Helminth Therapy
    • HDCs, safe, and effective Primobiotics
Additional Considerations: Diet, Anti-Inflammatories, and Immune Modulators

First, diet is most important as food is medicine. A child’s diet needs to include whole foods, that are as organic and non-processed as possible. It should include foods high in antioxidants such as berries, artichokes, kale, spinach, beets, dandelion greens, red cabbage and dark chocolate. Use herbs and spices, particularly garlic, ginger, oregano, turmeric and cinnamon, adding little sprinkles to anything. Healthy oils include extra virgin olive, avocado and coconut oil. Meats should be grass-fed organic and wild-caught fish. Drink lots of water. Remove additives, sugars, gluten, casein, soy, and any food sensitivities as much as possible. Basically, this is an anti-inflammatory, healthy diet that all of us should be attempting to attain.

Additionally, a healthy treatment protocol includes anti-inflammatories and antioxidants as listed below:

  • Anti-Inflammatories:
    • Ibuprofen (10 mg/kg every 6-8 hours in the short term as needed for flares)
    • Essential Fatty Acids–Omega 3 (EPA/DHA) and 6 (GLA)
    • Aloe
    • Curcumin
    • Flavonoids – Quercetin, Luteolin, Rutin
    • SPM
    • CBD or Hemp Oil
  • Antioxidants:
    • Vitamin D, A, and C
    • Zinc
    • Resveratrol
    • Melatonin
    • N-acetyl Cysteine and Glutathione

3. Interventions to Consider for Treatment of Symptoms (Anxiety/ OCD/Tics)

Below, you will find interventions for treating symptoms associated with PANDAS and PANS, such as anxiety, OCD, and tics.

  • Dietary Supplements:
    • 5-HTP
    • GABA
    • L-Theanine
    • Inositol
    • Magnesium
    • L-MTHF (if MTHFR mutation OR CFD)
    • Ashwagandha
    • Lemon Balm
    • Motherwort
    • Passionflower
    • Mimosa Bark
    • Hemp oil
    • N acetyl Cysteine/Glutathione
  • Exercise
  • Meditation and mantras
Other Interventions to Consider for the Treatment of Symptoms
  • Therapy
    • CBT (Cognitive Behavioral Therapy) or DBT (Didactic Behavioral Therapy) can be particularly effective for children and families with PANS/PANDAS
  • Removal of adenoids and tonsils
    • Important intervention for those with recurrent strep or sleep apnea
    • Also consider in certain cases where appropriate after discussing with your practitioner or referral to ENT familiar with PANDAS
  • Treatment of yeast, parasites, clostridia as well as mold, lyme and co-infections as indicated by history and physical exam and as warranted
  • Medications like SSRI’s (Prozac, Zoloft, etc) can often act as a “patch” for OCD or other symptoms
    • However, they should only be considered for short-term use in certain cases and starting with very low doses, increasing slowly if needed

Conclusion

PANS/PANDAS is a devastating autoimmune disorder in children that highlights another link between chronic and recurrent infection and immune dysregulation and neuropsychiatric and behavioral problems. Most importantly, this is a clinical diagnosis of an abrupt onset of symptoms.

Ongoing clinical experience and emerging research reveals the depth and scope of problems stemming from PANS/PANDAS. While OCD and tics are still common, other issues like anxiety, bedtime fears or sleep issues, enuresis or other urinary symptoms, aggression, and deficits in learning, attention, and social interaction are among the many manifestations that result from PANS/PANDAS and impair the daily functioning and cognitive progress for many children.

Heightened clinical suspicion and more appropriate and comprehensive treatment with antibiotics/antimicrobials and immune-modulating therapy will transform PANDAS from a devastating chronic illness with episodic flares into a treatable disorder.

About Nancy O'Hara, MD, MPH, FAAP

Dr. Nancy O’Hara is a board certified Pediatrician. Prior to her medical career, Dr. O’Hara taught children with autism. She graduated with highest honors from Bryn Mawr College and as a member of the Alpha Omega Alpha Honor Society from the University of Pennsylvania School of Medicine. She earned a Master’s degree in Public Health from the University of Pittsburgh. After residency, chief residency and general pediatric fellowship at the University of Pittsburgh, Dr. O’ Hara entered general private practice in 1993, and in 1998 began her consultative, integrative practice solely for children with special needs. Since 1999 she has dedicated her functional medicine practice to the integrative and holistic care of children with chronic illness and neurodevelopmental disorders such as ADHD, PANDAS/PANS, OCD, Lyme and ASD. She is also a leader in the training of clinicians, both in the United States and abroad.

For further information, see the references below and the following websites:

References:

Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am. J. Psychiatry 155(2), 264-271 (1998).

Swedo SE, Seidlitz J, Kovacevic M, et al. Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings. J. Child Adolesc. Psychopharmacol 25(1), 26-30 (2015).

Swedo SE, Leckman J, Rose N. From research subgroup to clinical syndrome: Modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). 2012;2:1-8. Pediatr. Therapeutics 2, 1-8 (2012).

Pavone P, Parano E, Rizzo R, et al. Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants. J. Child Neurol 21(9), 727-736 (2006).

Macerollo A, Martino D. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept. Tremor. Other Hyperkinet. Mov (N Y) 3 (2013).

Frankovich J, Thienemann M, Rana S, et al. Five youth with pediatric acute-onset neuropsychiatric syndrome of differing etiologies. J. Child Adolesc. Psychopharmacol 25(1), 31-37 (2015)

 Chang K, Frankovich J, Cooperstock M, et al. Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 201

3 PANS Consensus Conference. J. Child Adolesc. Psychopharmacol 25(1), 3-13 (2015).

Giedd JN, Rapoport JL, Garvey MA, et al. MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection. Am. J. Psychiatry 157(2), 281-283 (2000).

Frankovich J, Swedo S, Murphy T, et al. Clinical Management of Pediatric AcuteOnset Neuropsychiatric Syndrome: Part II-Use of Immunomodulatory Therapies. J. Child. Adolesc. Psychopharmacol 27(7), 574-593 (2017).

Murphy TK, Storch EA, Lewin AB, Edge PJ, Goodman WK. Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Pediatr. 2012;160(2):314–319.

Sigra S, Hesselmark E, Bejerot S. Treatment of PANDAS and PANS: a systematic review. Neurosci Biobehav Rev. 2018;86:51–65.

Cooperstock MS, Swedo SE, Pasternack MS, et al. Clinical management of pediatric acute-onset neuropsychiatric syndrome: part III-treatment and prevention of infections. J Child Adol Psychop. 2017;27:594–606.

Chang K, Frankovich J, Cooperstock M, et al. Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. J Child Adolesc Psychopharmacol. 2015;25:3–13.

Murphy ML, Pichichero ME. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med. 2002;156:356–361.

Maini  B,  Bathla  M,  Dhanjal  GS,  Sharma PD. Pediatric autoimmune neuropsychiatric disorders after streptococcus infection. Indian J Psychiatry 2012;54:375-7.


Thienemann, M et al. .Journal of Child and Adolescent Psychopharmacology.Sep 2017.566-573.http://doi.org/10.1089/cap.2016.0145

Swedo, S et al. .Journal of Child and Adolescent Psychopharmacology.Sep 2017.562-565.http://doi.org/10.1089/cap.2017.0042

Murphy T. K., Storch E. A., Lewin A. B., Edge P. J., Goodman W. K. Clinical factors associated with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. Journal of Pediatrics. The Journal of Pediatrics. 2012;160(2):314–319. 

Murphy T. K., Sajid M., Soto O., Shapira N., Edge P., Yang M., et al. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biological Psychiatry. 2004;55(1):61–68. 

Murphy T. K., Snider L. A., Mutch P. J., Harden E., Zaytoun A., Edge P. J., et al. Relationship of movements and behaviors to Group A Streptococcus infections in elementary school children. Biological Psychiatry. 2007;61(3):279–284.

Luo F., Leckman J. F., Katsovich L., Findley D., Grantz H., Tucker D. M., et al. Prospective longitudinal study of children with tic disorders and/or obsessive-compulsive disorder: relationship of symptom exacerbations to newly acquired streptococcal infections. Pediatrics. 2004;113(6):e578–e585. 

Leslie D. L., Kozma L., Martin A., Landeros A., Katsovich L., King R. A., et al. Neuropsychiatric disorders associated with streptococcal infection: A case-control study among privately insured children. Journal of the American Academy of Child and Adolescent Psychiatry. 2008;47(10):1166–1172.

Macerollo A, Martino D. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an evolving concept. Tremor other Hyperkinet Mov. N Y. 2013:3.

Calaprice D, Tona J, Murphy TK. Treatment of pediatric acute-onset neuropsychiatric disorder in a large survey population. J Child Adolesc Psychopharmacol. 2018;28(2):92–103.

Frankovich J, Thienemann M, Rana S, Chang K. Five youth with pediatric acute-onset neuropsychiatric syndrome of differing etiologies. Journal of Child and Adolescent Psychopharmacology. 2015;25(1):31–7.

Calaprice, D et al. .Journal of Child and Adolescent Psychopharmacology.Mar 2018.92-103.http://doi.org/10.1089/cap.2017.0101

Murphy  TK, Sajid  M, Soto  O,  et al.  Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics.  Biol Psychiatry. 2004;55(1):61-68.

Allen, Albert J. et al. Case Study: A New Infection-Triggered, Autoimmune Subtype of Pediatric OCD and Tourette's Syndrome. Journal of the American Academy of Child & Adolescent Psychiatry, Volume 34, Issue 3, 307 - 311

Giulino  L, Gammon  P, Sullivan  K,  et al.  Is parental report of upper respiratory infection at the onset of obsessive-compulsive disorder suggestive of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection?  J Child Adolesc Psychopharmacol. 2002;12(2):157-164.

Leslie  DL, Kozma  L, Martin  A,  et al.  Neuropsychiatric disorders associated with streptococcal infection: a case-control study among privately insured children.  J Am Acad Child Adolesc Psychiatry. 2008;47(10):1166-1172.

Mell  LK, Davis  RL, Owens  D.  Association between streptococcal infection and obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder.  Pediatrics. 2005;116(1):56-60.

Bessen DE, Lombroso PJ (in press): Group A streptococcal infections and their potential role in neuropsychiatric disease. Adv Neurol.

Touwen BCL: Examination of the Child With Minor Neurological Dysfunction. Clinics in Developmental Medicine, vol 71. London, Heinemann, 1979, p 53

Denckla MB: Revised neurological examination for subtle signs. Psychopharmacol Bull 1985; 21:773–793

Brandenburg NA, Friedman RM, Silver SE: The epidemiology of childhood psychiatric disorders: prevalence findings from recent studies. J Am Acad Child Adolesc Psychiatry 1990; 29:76–83

Swedo SE, Leonard HL, Mittleman BB, Allen AJ, Rapoport JL, Dow SP, Kanter ME, Chapman F, Zabriskie J: Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. Am J Psychiatry 1997; 154:110–112

Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: Hypothesis or entity? Practical considerations for the clinician. Pediatrics 2004;113;883-6.

Garvey M. A. Giedd J. Swedo S. E. PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. Journal of Child Neurology 1998;13(9): 413–423. [PubMed: 9733286 ]

Bernstein G. A. Victor A. M. Pipal A. J. Williams K. A. Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood obsessive-compulsive disorder. Journal of Child and Adolescent Psychopharmacology 2010;20(4):333–340. [PubMed: 20807071]

Toufexis, M. D., Hommer, R., Gerardi, D. M., Grant, P., Rothschild, L., D’Souza, P., Williams, K., Leckman, J., Swedo, S. E., & Murphy, T. K. (2015). Disordered Eating and Food Restrictions in Children with PANDAS/PANS. Journal of Child and Adolescent Psychopharmacology, 25(1), 48–56. https://doi.org/10.1089/cap.2014.0063


*All content of this article is for informational purposes only. Furthermore, it is not a substitute for professional advice, diagnosis, or treatment. For this reason, always seek the advice of your physician, therapist, or other qualified health provider with any questions or concerns you may have.