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Disease Profile

Pediatric acute-onset neuropsychiatric syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PANS

Summary

Pediatric acute-onset neuropsychiatric syndrome (PANS) is a condition defined by sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms.[1] Examples of other symptoms include anxiety, depression, tics, personality changes, decline in school performance, and sensory sensitivities.[2][3] Symptoms typically begin during childhood but may begin at any age.[4] Symptoms may go away for a while and then come back (referred to as a relapsing and remitting course).[1] However, symptoms may be worse and last longer with each episode.[5]

PANS is thought to have a variety of possible causes. In more than 80% of cases, there is evidence of an abnormal autoimmune or inflammatory response in the brain following any of various infections in the body.[1][6] When the associated infection is known to be strep, the condition is called PANDAS (a subtype of PANS).[2] Other possible causes of PANS include psychological trauma and underlying autoimmune, neurological, endocrine, or metabolic disorders.[1] There are likely non-infectious triggers that have not yet been identified.[2]

The diagnosis of PANS is made only when all other possible causes of symptoms are ruled out (this is a called a diagnosis of exclusion). Depending on the symptoms present, this process may rely on factors such as medical and psychiatric history, a physical exam, evaluation by various specialists, and a variety of tests or imaging studies such as blood tests, an electroencephalogram (EEG), sleep study (polysomnography) and/or brain MRI.[1]

Treatment depends on the symptoms and severity in each person and may involve improving symptoms with psychiatric medicines and behavioral interventions, treating underlying infections or sources of inflammation with antibiotics, and/or stabilizing the immune system with immunotherapy and/or anti-inflammatory therapies (in immune-related PANS).[1] Treatment may be tapered down or stopped when symptoms resolve but may be needed again if symptoms return.[1]

Many people with PANS who undergo treatment show overall improvement over months to years or will recover completely.[7][8] However, relapses may still occur after long periods of remission.[8] Others will have ongoing symptoms that require continuous treatment.[7] If not treated, PANS can lead to permanent debilitation.[5] Unfortunately, at this time it is not possible to predict the course of the condition in each person.[7]

Symptoms

Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by the sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms (also with sudden onset).[1] Symptoms typically begin during childhood but may begin at any age.[4] Any or several of many obsessive-compulsive symptoms typically develop abruptly (within one to two days). New symptoms may arise and initial symptoms may worsen over the next few days or weeks. Eating restrictions may involve refusing to eat specific foods or all foods.[4]

Other symptoms that begin at the same time as obsessive compulsive symptoms or eating restrictions may include:[4][9]

  • Anxiety such as extreme anxiety or worry, irrational fears, and/or panic attacks
  • Emotional lability (excessive moodiness or inappropriate emotional responses) and/or depression, which may cause suicidal thoughts or self-injury
  • Irritability, aggression, and/or severe oppositional behaviors (consistent, uncooperative and hostile behaviors)
  • Behavioral (developmental) regression such as an abrupt increase in temper tantrums and loss of age-appropriate language skills and behaviors
  • Sudden deterioration in school performance such as short attention span, difficulty concentrating, or decrease in math reasoning
  • Motor or sensory abnormalities such as worsening handwriting, tics, clumsiness, involuntary movements, and increased sensitivity of the senses
  • Somatic signs and symptoms complaints of symptoms for which no medical cause can be found, such as sleep disturbances (night terrors and/or trouble sleeping), bedwetting, or frequent urgency to urinate (when no urinary tract infection is present)

In some cases, symptoms of PANS go away for a while and then come back (this is referred to as a relapsing and remitting course).[1] However, symptoms may be worse and last longer with each episode.[5] In other cases, symptoms last for months or years (are chronic) or get progressively worse over time.[10]

Many symptoms of PANS can be a feature of a variety of known neurological, psychiatric, or medical disorders, so the diagnosis of PANS requires that all other possible causes of symptoms have been ruled out.[1][4][9] The abruptness and presence of more than one symptom is largely what sets PANS apart from psychiatric conditions with overlapping symptoms.[9]

Cause

PANS is thought to have a variety of possible causes. More than 80% of cases are thought to result from an abnormal autoimmune or inflammatory response in the brain following some type of infection.[1] When the infection is known to be strep, a person is diagnosed with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), a subtype of PANS.[2] It is not yet known why some children get PANDAS after a strep infection while others do not.[11] Other types of infections that may trigger symptoms of PANS include upper respiratory infections, influenza, chickenpox, mycoplasma, and Lyme disease.[6][8]

Other possible causes of PANS include psychological trauma as well as underlying autoimmune, neurological, endocrine, or metabolic disorders.[1] Examples include cerebral vasculitis (inflammation of blood vessels in the brain) and neuropsychiatric lupus.[1] There are thought to be various non-infectious triggers that have not yet been identified.[2] Additionally, future episodes of symptoms may be caused by triggers different from the trigger of the previous episodes.[5] Of note, identifying a trigger is not required for a diagnosis of PANS.[11]

Diagnosis

PANS is a clinical diagnosis, which means the diagnosis is based on the signs, symptoms and medical history rather than laboratory testing or imaging studies (although these are used to rule out other health problems). The current recommended criteria for a diagnosis of PANS include:[4][9]

  • Sudden and severe onset of obsessive compulsive disorder or severely restricted food intake (appearing and worsening within 24-48 hours) 
  • Simultaneous sudden and severe onset of at least two of the following additional neuropsychiatric symptoms:
    • Anxiety
    • Emotional lability (rapid changes in mood or emotion) and/or depression
    • Irritability, aggression, and/or severely oppositional behaviors
    • Behavioral (developmental) regression (loss of previously acquired skills or age-appropriate behavior)
    • Deterioration in school performance (e.g. symptoms of ADHD, memory deficits, or cognitive changes)
    • Sensory or motor abnormalities
    • Somatic signs and symptoms various symptoms for which no medical explanation can be found, such as sleep disturbances, involuntary urination, or urinary frequency
  • Symptoms are not better explained by a known neurologic or medical disorder. The diagnosis of PANS should be made only when all other possible neurological or medical causes of symptoms are ruled out. This is a called a diagnosis of exclusion. Depending on symptoms present, examples of disorders to rule out may include obsessive-compulsive disorder, Tourette syndromeSydenham chorea, autoimmune encephalitis, neuropsychiatric lupuscentral nervous system vasculitis, and other disorders.[1]

Ruling out other conditions in order to diagnosis PANS may rely on:[1][9]

  • A comprehensive medical history (including infection history) and physical exam. These should not focus only on identifying signs and symptoms of PANS, but on identifying and ruling out features of other disorders that cause similar symptoms.
  • Family history, with particular focus on neurologic diseases, mental health conditions, autoimmune and autoinflammatory diseases, immunodeficiency disorders, and frequent infections.
  • Psychiatric evaluation (individual PANS symptoms overlap with a variety of psychiatric disorders) and mental status exam.
  • Various blood tests, urinalysis, throat culture, and/or cerebrospinal fluid analysis.
  • Infectious disease evaluation (most cases of PANS are suspected to occur following an infection, particularly strep in those with the PANS subtype PANDAS).
  • Evaluation for autoimmune and autoinflammatory diseases (some of which can cause neuropsychiatric symptoms) and immunodeficiency.
  • Additional tests such as brain MRI, an electroencephalogram (EEG), sleep study (polysomnography), and/or swallowing study (for those with restricted food intake).

Detailed recommendations from the 2013 PANS Consensus Conference regarding evaluation and diagnosis can be viewed here.

Treatment

Treatment of pediatric acute-onset neuropsychiatric syndrome (PANS) depends on the specific symptoms, severity, and cause (if known) in each person. Initial treatment may depend on which symptoms most impair daily living and create the most distress.[1] It is recommended that treatment begin as soon as the diagnosis is made. Treatment may involve the following, either alone or in combination:[1][7][8][10]

  • Treating symptoms with psychiatric medications (when appropriate), psychotherapy (particularly cognitive behavioral therapy), and supportive interventions (such as school accommodations, family support, and maintaining nutrition and hydration needs with restricted food or fluid intake). Some interventions may take several weeks to begin helping and may require adjustments, as symptoms frequently change during the course of the condition. The experiences of healthcare professionals who treat PANS suggest that specific symptoms of PANS (such as anxiety and obsessive-compulsive symptoms) respond to the same medications used to treat these symptoms in people without PANS. 
  • Treating underlying infections or sources of inflammation with antibiotics. An initial course of anti-strep antibiotics is recommended in all cases, even when there is not a documented infection. Some people with PANS have experienced complete and lasting remission of symptoms during treatment with antibiotics. Using antibiotics long-term to prevent infections (prophylaxis) may be recommended for children with PANDAS who have severe neuropsychiatric symptoms or recurrent strep-associated flares of symptoms.
  • Stabilizing the immune system with immunotherapy and/or anti-inflammatory therapies (in immune-related PANS).[1] These therapies should be used only in cases where there is evidence of inflammation in the nervous system (neuroinflammation) or post-infectious autoimmunity (misdirected immune responses).[10] Depending on symptoms and severity, therapy options may include nonsteroidal anti-inflammatory drugs, corticosteroids, and intravenous immune globulin (IVIG) or other nonsteroidal immunotherapies.[10] Once started, immunotherapy should only continue if it is clear that symptoms are improving.[1] 

Treatment may be tapered down or stopped completely when symptoms resolve, but may be needed again if symptoms return (when treatment is stopped or at some time later).[1] Many people with PANS will recover completely and discontinue some or all treatments. However, others will have ongoing symptoms that require continuous treatment.[7] If not treated, PANS can lead to permanent debilitation.[5]

In most cases, a child's primary care provider can effectively treat symptoms of PANS. Children with severe or life-threatening symptoms may need specialized treatment coordinated by a team of PANS specialists.[1]

Detailed treatment recommendations for healthcare providers are available and can be accessed in our Learn More section under Selected Full-Text Journal Articles.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • KidsHealth from Nemours has an information page on Pediatric acute-onset neuropsychiatric syndrome. Click on the link to access this resource.
    • The National Institute of Mental Health (NIMH) has information on this topic. NIMH is part of the National Institutes of Health and is dedicated to understanding, treating, and preventing mental illnesses.
    • The PANDAS Network offers an information page on Pediatric acute-onset neuropsychiatric syndrome. Please click on the link to access this resource.
    • The PANDAS Physicians Network provides information about PANS and PANDAS.

      Selected Full-Text Journal Articles

        References

        1. Swedo SE, Frankovich J, Murphy TK. Overview of Treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome. J Child Adolesc Psychopharmacol. September, 2017; 27(7):562-565. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610386/.
        2. What is PANS?. PANDAS Network. https://www.pandasnetwork.org/understanding-pandaspans/what-is-pans/. Accessed 9/27/2018.
        3. Pichichero ME. PANDAS: Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci. UpToDate. Waltham, MA: UpToDate; June 7, 2018; https://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci.
        4. PANDAS Physician Network. PANS: PPN Diagnostic Guidelines. https://www.pandasppn.org/ppn-pans-diagnostic-guidelines/. Accessed 9/28/2018.
        5. PANS/PANDAS Fact Sheet. PANDAS Network. 2016; https://www.pandasnetwork.org/wp-content/uploads/2016/04/2016-PNETWORK-fact-.pdf.
        6. Ben-Joseph EP. What is "PANS?". KidsHealth from Nemours. September, 2015; https://kidshealth.org/en/parents/pandas.html.
        7. Thienemann M, Murphy T, Leckman J, et al. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I—Psychiatric and Behavioral Interventions. J Child Adolesc Psychopharmacol. September 1, 2017; 27(7):566–573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610394/.
        8. Cooperstock MS, Swedo S, Pasternack MS, Murphy TK. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part III—Treatment and Prevention of Infections. J Child Adolesc Psychopharmacol. September, 2017; 27(7):https://www.liebertpub.com/doi/full/10.1089/cap.2016.0151.
        9. 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. February, 2015; 25(1):3-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340805/.
        10. Frankovich J, Swedo S, Murphy T, et al. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II—Use of Immunomodulatory Therapies. J Child Adolesc Psychopharmacol. September, 2017; 27(7):https://www.liebertpub.com/doi/full/10.1089/cap.2016.0148.
        11. What are PANS and PANDAS?. PANDAS Physicians Network. https://www.pandasppn.org/what-are-pans-pandas/. Accessed 10/1/2018.
        12. Information About PANS/PANDAS. National Institute of Mental Health. https://www.nimh.nih.gov/labs-at-nimh/research-areas/clinics-and-labs/sbp/information-about-pans-pandas.shtml. Accessed 9/28/2018.

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