User:Buster23/PANS draft

PANS is an acronym for Pediatric Acute-Onset Neuropsychiatric Syndrome. This diagnosis is used to describe children who have "abrupt, dramatic onset of obsessive-compulsive disorder (OCD) or severely restricted food intake" coincident with the presence of two or more neuropsychiatric symptoms.

Classification
PANS is a clinical diagnosis defined as a subset of pediatric onset obsessive-compulsive disorder (OCD). It is distinguished from traditional childhood onset OCD by the severity, abruptness and dramatic onset of symptoms.

Identification
Children and adolescents with PANS are clinically identified by the following three criteria: "
 * 1. Abrupt, dramatic onset of obsessive-compulsive disorder 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
 * * Anxiety
 * * Emotional lability and/or depression
 * * Irritability, aggression and/or severely oppositional behaviors
 * * Behavioral (developmental) regression
 * * Deterioration in school performance
 * * Sensory or motor abnormalities
 * * 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 chorea, systemic lupus erthematosus, Tourette disorder or others."

There are other conditions that may have similar presentation. Diagnostic workup of patients suspected of PANS should exclude Sydenham Chorea, Lupus Erythematosus, Acute disseminated encephalomyelitis and Tourettes Syndrome.Evidence of Acute Rheumatic Fever is exclusionary to PANS diagnosis.

Based on the concurrent neuropsychiatric symptoms, the physician will run other diagnostic tests which may include MRI scan, lumbar puncture, and electroencephalogram.

Acute and Dramatic Onset of obsessive-compulsive disorder
The main distinguishing symptom of PANS is the acute and dramatic onset of obsessive-compulsive disorder in a toddler, child or adolescent. Parents are often able to "identify the exact date and time that their children's symptoms had begun". Parents describe the onset as "'ferocious', 'overwhelming' or 'severe enough that we took him to the ER'". They describe their child as "'possessed' by the illness over the course of just a few days". While there is uniformity in the intensity of onset, the presentation of symptoms can be quite varied with some symptoms present at onset and others emerging over weeks.

Obsessions
An obsession is an unwelcome thought or idea that recurs and does not go away despite efforts to ignore or confront them. In children, obsessions can be difficult to determine but are often associated with contamination (such as worrying about germs from others), fear of throwing up or choking, fear of hurting oneself or others (e.g., fear of scissors, knives or other sharp objects), violent or horrific images (e.g., images of murders or dismembered bodies), fear of throwing away unimportant items, and excessive concern about having blasphemous thoughts.

Compulsion
A compulsion is a ritual or a behavior that the child feels must be performed. Often the compulsion is in response to an obsession and the child feels the ritual must be completed to avoid the feared result of the obsession. Compulsive behavior in children often takes known patterns such as "needing to excessively confess for minor or imagined transgressions" or "excessive touching, tapping, rubbing" particularly a surface such as a doorway, needing to arrange objects until they feel "just right", and counting rituals. Of particular note in children are rituals that involve their parents such as excessive reassurance or repeatedly asking the parent to answer the same question.

Severely restricted food intake
Food restriction is called out as a separate symptom in PANS because it is sometimes the only sign of an underlying compulsion associated with a food obsession. In children with PANS, there are often preoccupations with the "texture of food and a fear of choking, vomiting or contamination from ingesting specific foods."

Concurrent presence of at least 2 additional sudden onset/acute neuropsychiatric symptoms
In addition to the sudden onset OCD, PANS requires two additional neuropsychiatric conditions. It should be noted that these conditions also have sudden onset and are of a dramatic nature considerably outside the norm for children.

Anxiety
While the anxiety may take a number of forms, severe separation anxiety, fear of weather related events and severe social anxiety are the most common presentation in PANS children. The child may appear "terror stricken" and excessively vigilant as if confronted by a constant threat. Children may exhibit a fight or flight reaction. Anxiety can be so severe as to cause panic attacks in children. Children with severe separation anxiety display a clutchy/clinging behavior and are unable to be away from their parent (or in rare cases an object or a room in a home).

Emotional lability and depression
Emotional labile children have sudden and unexpected changes in mood states shifting from laughter to tears without obvious cause. Some children may experience the abrupt onset of clinical depression that can be severe enough to be accompanied by suicidal ideation.

Agression, irritability and oppositional behaviors
The oppositional behaviors are present throughout the day and the aggression occurs without provocation. Most notable is the sharp contrast of this behavior from the pre-onset behavior where the child is usually described as "sweet tempered and well-liked". It should be noted that irritation occurring because a ritual has been interrupted are not counted in this category.

Behavioral (developmental) regression
This regression is inconsistent with the child's chronological age and their previous stage of development. Parents often note a sudden return of "baby talk" and socially inappropriate behavior to their age.

Sudden deterioration in school performance and learning abilities
While this is a broad category, most parents report a specific loss in math or visuospatial skills and other disturbances in executive functioning. Chronic conditions such as ADHD or a learning disability are not counted here nor are motor abnormalities common with a tic disorder or the erasures associated with childhood-onset OCD.

Sensory abnormalities
Many patients report a sudden increased sensitivity to light or noise. In addition, they may exhibit particular difficulties with how clothing feels. Examples are a child that wakes up and can no longer wear socks or underwear or their favorite jeans. Often these children are unable to sit still. Often they use pressure, spinning, or sitting upside down to calm a sense of "wrongness". Visual hallucinations are also commonly reported (such as floating bubbles). These are sometimes ascribed to ocular migraines.

Motor abnormalities
Dysgraphia and sudden clumsiness are often described as symptoms here. Handwriting once legible becomes illegible. Drawn figures are no longer recognizable. Other movement disorders that have a sudden onset are counted in this category as well.

Somatic signs and symptoms
Disturbances in urination and daytime urinary frequency are commonly reported in PANS children.

Proposed mechanism
PANS is a clinical diagnosis and as such is defined by the presentation of symptoms and not a particular etiology or cause. However, there is active research in the hypothesis that these neuropsychiatric symptoms are a result of antibodies formed in response to an infection (PITAND) and specifically antibodies formed as a response to a group-A beta hemolytic streptococcal infection (PANDAS). There may, however, be non-infection causes of PANS.

Management
As with the general class of OCD, patients and parents get significant value in having supportive therapies for addressing rituals and disruptive behaviors. While children and toddlers may lack the insight necessary for participation in Cognitive Behavioral Therapy (CBT), the supportive tools are often helpful for parents to break out of rituals, help the children through their anxieties, and in managing future exacerbations. A particular form of Cognitive Behavioral Therapy is Exposure and Ritual Response Prevention (ERP) that is a form of exposure therapy.

Not associated with Infection
In children for whom no infection trigger can be identified, the treatment is primarily one of treating symptoms. Selective Serotonin Reuptake Inhibitors (SSRI) have been used with some success; however, the treating clinicians should "Start Low and Go Slow!" as there have been reports that children with PANS are exquisitely sensitive to psychotropic medications.

Associated with Infection
If a child fulfills the clinical criteria for PANS, the possibility of an infectious trigger should also be considered and evaluated. Common laboratory testing includes a rapid throat culture, AGAR plate culture, check for peri-anal strep, and mycoplasma pneumonia. If a child presents with a rapid throat culture, current AMA recommendation is to treat this as an infection and place the child on antibiotics. Studies indicate that compliance on penicillin is challenging with children. Other studies have found better compliance when blister packs or when once daily antibiotics were used.

Blood tests may also be used to check for a prior streptococcal infection; however, the accuracy and sensitivity of these tests has been recently questioned by two longitudinal studies that indicate Antistreptolycin-O antibody titer failed to rise in 46% and 52% of cases respectively despite positive cultures and confirmed infection.

Experimental Treatments
There was a small study in 1998 on the use of intravenous immunoglobulin (IVIG) and plasma exchange showing efficacy at reducing symptom severity. A Turkish study found similar improvements using plasma exchange. The National Institute for Mental Health (NIMH) considers these treatments to be reserved for "critically ill patients". The NIMH is currently running trials to replicate the 1998 study to assess the impact of IVIG on symptoms.

History

 * 1894 : Sir William Osler publishes on Chorea and Choreiform Affections separated Sydenham Chorea from Huntington's disease finding that Sydenham Chorea was associated with rheumatic fever whereas Huntington's disease was an inherited disease.
 * 1964 : Freeman publishes The Emotional Correlates of Sydenham's Chorea in which he found 75% of patients with Sydenham's Chorea were found to have psychiatric disturbances and while the chorea remitted, the psychiatric symptoms did not.
 * 1976 : Husby publishes Antibodies Reacting with Cytoplasm of subthalamic and Caudate Nuclei Neurons in Chorea and Acute Rheumatic Fever and Anti-neuronal Antibody in Sydenham's Chorea in which he finds that specific antibodies cross react in 46% of children with rheumatic chorea.
 * 1989 : Swedo publishes Obsessive-Compulsive Disorder in Children and Adolescents : Clinical Phenomenology of 70 Consecutive Cases in which she finds remarkable similarity in the pattern of OCD symptoms and the likelihood of an etiologic basis.
 * 1989 : Khanna publishes that a created monoclonal antibody (D8/17) distinguishes cells from patients with rheumatic fever.
 * 1993 : Bronze and Dale publish their findings that antibodies to streptococcal M-protein cross react with neuronal tissue.
 * 1994 : Swedo publishes a commentary in Pediatrics on the likelihood that neuropsychiatric onset in children may be due to antineuronal antibodies.
 * 1995 : Allen and Swedo found 4 children with sudden onset OCD associated with infections (2 with GABHS and 2 with viral infections). On theory of antibody cross-reactivity, they used IVIG, prednisone and PEX and found all three methods effective.  They called this treatable subset of OCD pediatric infection triggered autoimmune neuropsychiatric disorder (PITAND).
 * 1997 : Swedo used the monoclonal antibodies from Khanna's work and found that the monoclonal antibody differentiated children who exhibited sudden and dramatic onset of neuropsychiatric symptoms and children with Sydenham chorea differentiated from controls. She introduced the term PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) to distinguish this work as focusing on a the group-A Beta-hemolytic streptococcal infection.
 * 1998 : In this year, Swedo published the clinical presentation of 50 cases and defined the PANDAS criteria. Criticisms of the criteria were almost immediate commenting that the criteria was insufficient to separate the PANDAS subgroup from children with Tourettes.
 * 1999 : Perlmutter and Swedo conducted a blinded placebo controlled study on children who met the PANDAS criteria showing significant improvement to treatment with IVIG or Plasma Exchange (PEX)( improvement of 45% and 50% respectively).
 * 2000: Nicolson and Swedo ran a second trial and determined that IVIG and Plasma Exchange were not effective for patients whose onset was not coincident with infection or did not meet the PANDAS criteria.
 * 2000 : Also in 2000, Madeline Cunningham (a microbiologist) publishes Pathogenesis of Group A Streptococcal Infections. and specifically finds that a monoclonal antibody from rheumatic carditis recognizes heart valves and laminin.
 * 2003 : In 2003, Kirvan and Swedo join with Cunningham and publish Mimicry and Autoantibody-mediated neuronal cell signaling in Sydenham chorea isolating 3 antibodies that cross-react with neuronal tissue. In addition, Kirvan notes that CaM kinase II is induced by these antibodies isolated in Sydenham chorea.
 * 2004 : Several commentaries are written raising questions whether the PANDAS criteria are sufficiently tight to properly define a subgroup of patients whose symptoms have distinct etiologies.  Swedo responds to these commentaries and clarifies the clinical presentation of PANDAS and specifically the distinguishing acute onset and episodic course.
 * 2006: Kirvan and Swedo find serum differences between children matching the PANDAS criteria and children with childhood onset OCD or Tourettes.
 * 2008: Kurlan publishes result of a two year longitudinal study of children with Tourettes showing that these patients (who also fit the PANDAS criteria) "may be susceptible to GABHS infection as a precipitant of their symptoms." However, the authors also noted that GABHS infection was not the most common precipitant of exacerbations.
 * 2008 Singer publishes serum antibody findings on a subset of the patients from Kurlan's longitudinal study and finds no differences from controls. . This paper, however, was criticized for not having selected children with acute onset.
 * 2009: Hornig and Yaddanapudi announce that behavioral changes can be affected in mice by tansferring antibodies created in response to Group A Beta Hemolytic strep.
 * 2009: Bartholomäus is able to show how the blood-brain barrier is crossed by activated T-cells producing inflammation.
 * 2011: Leckman publishes a longitudinal study of 31 patients classified as meeting the PANDAS criteria who did not show any differences from control in exacerbations to GABHS infections. This paper was criticised however, for not having selected patients matching the sudden onset criteria.
 * 2011: Singer proposes moving from PANDAS to Childhood Acute Neuropsychiatric Syndrome (CANS).
 * 2012: Swedo and Leckman publish "From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) where sudden onset OCD is the primary distinguishing features and tic disorders are moved to one of the coincident neuropsychiatric symptoms.  Dr. Swedo explains that the team modified the PANDAS criteria to clarify the presentation and "eliminate etiologic factors."