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PANS AND PANDAS

Mats Johnson provides a detailed account of what PANDAS/PANS is, along with treatment.

What is PANDAS?

The term PANDAS stands for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. It was introduced by researchers at the American National Institute of Mental Health (NIMH) in the 1990’s; diagnostic criteria were published by Swedo in 1998. According to early descriptions, the condition typically manifests suddenly with sudden and dramatic onset of OCD (Obsessive Compulsive Disorder) and/or tics culminating within the space of 24 to 48 hours, accompanied by a host of other neuropsychiatric symptoms, e.g. hyperactivity, severe anxiety/separation anxiety, irritability, temper tantrums, light or sound sensitivity, urinary urge incontinence, regression in terms of development and motor skills (handwriting/drawing) and abnormal movements. The condition was said to occur in conjunction with streptococcal infections, mainly in pre-pubescent children.

Streptococcal infections were singled out because previously known diseases were associated with these bacteria (rheumatic fever and Sydenham’s chorea). Rheumatic fever is an inflammatory disease affecting the heart, joints, skin and brain. Sydenham’s chorea is a neurological condition with irregular involuntary movements of e.g. arms, legs and torso, similar to what one would find in cases of rheumatic fever. However, the link between streptococcal infections and PANDAS has proven difficult to corroborate definitively, as there have been reports of cases with similar symptoms following other infections. Neuroinflammatory or immunological mechanisms have been suggested, but no definitive biomarkers have been found as of yet. Studies have produced varying results, leading the diagnosis to become controversial.

Author

Mats Johnson

PANS

This led to a research group at NIMH creating new diagnostic criteria for PANS (Pediatric Acute-onset Neuropsychiatric Syndrome), which focused entirely on the symptomatology and not on the cause (Swedo et al. 2012).

Criteria for PANS

1. Acute, dramatic onset of OCD or severely restricted food intake.

2. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and acute onset, from at least two of the following seven categories:
a. Anxiety
b. Emotional lability and/or depression
c. Irritability, aggression and/or severely oppositional behaviours
d. Behavioural (developmental) regression
e. Deterioration in school performance
f. Sensory or motor abnormalities
g. Somatic signs and symptoms, including sleep disturbances, enuresis or urinary frequency

3. Symptoms are not better explained by a known neurologic or medical disorder, such as Sydenham’s chorea, systemic lupus erythematosus, Tourette syndrome or others. Note that the diagnostic work-up of patients suspected of PANS must be comprehensive enough to rule out these and other relevant disorders. The nature of the co-occurring symptoms will dictate the necessary assessments, which may include MRI scan, lumbar puncture, electroencephalogram or other diagnostic tests.

The researchers strongly emphasised the point that other known neurological and medical conditions must first be eliminated, e.g. autoimmune encephalitis, systemic autoimmune disease, metabolic diseases, epilepsy. In order to differentiate the condition from OCD and other psychiatric conditions like anxiety disorder, depression/bipolar disorder, Tourette syndrome, trauma/stress syndrome (which might also have quite acute onset), it was established that the PANS diagnosis should be limited to cases with acute onset of symptoms from multiple domains (Chang et al. 2015, Swedo et al. 2017). Several PANS/PANDAS cohorts have recently also been described in Sweden (Hesselmark et al. 2017, Gromark et al. 2019, Johnson et al. 2019).

Treatment

Guidelines for treatment of PANS/PANDAS have been published by the PANS Research Consortium (PRC) in the U.S. (Swedo et al. 2017, Cooperstock et al. 2017, Frankovich et al. 2017, Thienemann et al. 2017), based on many years of clinical experience and research. The National Board of Health and Welfare established Swedish guidelines (2017), deemed the available scientific evidence insufficient and therefore recommended that diagnosis and treatment should be handled as part of Research and Development (R&D). Clinical guidelines have also been published by Karolinska University Hospital (2018).

The PRC recommends that treatment be tailored according to each specific patient’s needs, symptomatology and trajectory, focusing on both alleviating symptoms and treating suspected causes of the symptoms. Antibiotics are recommended in cases of suspected or verified bacterial infection. Information, support and psychotherapy (e.g. CBT), as well as psychopharmaceutical treatment of more severe symptoms, are recommended at an early stage in order to lessen the burden of the symptoms. Anti-inflammatory treatment (NSAIDs or cortisone drugs) have been used in cases with mild to moderate symptoms, while immunomodulating treatment, for example intravenous immunoglobulin therapy (IVIG), has been used to treat individuals with more severe symptoms.

The complex symptomatology and the importance of medical and psychiatric differential diagnosis call for close collaboration between many different specialties (child psychiatry/neuropsychiatry, child neurology/medicine, immunology/rheumatology). There is a need for multidisciplinary teams and international collaboration, as well as more research regarding diagnosis and treatment.

At the GNC, a unique study of treatment efforts for PANS, including immunoglobulin/IVIG, has been ongoing since 2020; the study is conducted within the so-called OPHELIA project

REFERENCES

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

Cooperstock MS et al. (2017). Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part III—Treatment and Prevention of Infections. J Child Adolesc Psychopharmacol 27:594–606.

Frankovich J et al. (2017). Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II—Use of Immunomodulatory Therapies. J Child Adolesc Psychopharmacol 27:574–593.

Gromark et al. (2019). Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet, J Child Adolesc Psychopharmacol 29:625-633.

Hesselmark E, Bejerot S (2017). Biomarkers for diagnosis of pediatric acute neuropsychiatric syndrome (PANS)—sensitivity and specificity of the Cunningham Panel. J Neuroimmunol 312:31–37.

Johnson M et al. (2019). Paediatric acute-onset neuropsychiatric syndrome in children and adolescents: an observational cohort study. Lancet Child Adolesc Health 3:175-180.

Karolinska Universitetssjukhuset (2018). Rutiner för handläggning av barn med misstänkt PANS (inklusive PANDAS).

Socialstyrelsen (2017). Nationella riktlinjer för vård vid depression och ångestsyndrom. https://www.socialstyrelsen.se/publikationer2017/2017-12-4 (accessed Dec 22, 2019).

Swedo SE et al. (1998). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases. Am J Psychiatry 155:264–271.

Swedo SE et al. (2012). From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Therapeut 2:113–21.

Swedo SE et al. (2017). Overview of treatment of pediatric acute-onset neuropsychiatric syndrome. J Child Adolesc Psychopharmacol 27:562–65.

Thienemann M et al. (2017). Clinical management of pediatric acute-onset neuropsychiatric syndrome: part I—psychiatric and behavioral interventions. J Child Adolesc Psychopharmacol 27:566–73.