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). Symptoms typically begin during childhood but may begin at any age. 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.

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

• 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). However, symptoms may be worse and last longer with each episode. In other cases, symptoms last for months or years (are chronic) or get progressively worse over time.

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. The abruptness and presence of more than one symptom is largely what sets PANS apart from psychiatric conditions with overlapping symptoms.

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:

• 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 syndrome, Sydenham chorea, autoimmune encephalitis, neuropsychiatric lupus, central nervous system vasculitis, and other disorders.

Ruling out other conditions in order to diagnosis PANS may rely on:

• 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).

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. It is recommended that treatment begin as soon as the diagnosis is made. Treatment may involve the following, either alone or in combination:

• 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). 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). Depending on symptoms and severity, therapy options may include nonsteroidal anti-inflammatory drugs, corticosteroids, and intravenous immune globulin (IVIG) or other nonsteroidal immunotherapies. Once started, immunotherapy should only continue if it is clear that symptoms are improving.

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). Many people with PANS will recover completely and discontinue some or all treatments. However, others will have ongoing symptoms that require continuous treatment. If not treated, PANS can lead to permanent debilitation.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.