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Information About PANS/PANDAS

General Information

PANDAS is an abbreviation for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. The term is used to describe a subset of children and adolescents who have Obsessive Compulsive Disorder (OCD) and/or tic disorders, and in whom symptoms worsen following strep. infections such as "Strep throat" and Scarlet Fever.

PANS is a newer term used to describe the larger class of acute-onset OCD cases. PANS stands for Pediatric Acute-onset Neuropsychiatric Syndrome and includes all cases of acute onset OCD, not just those associated with streptococcal infections.

Background & History

In the early 1990’s, investigators at the National Institute of Mental Health (Drs. Susan Swedo, Henrietta Leonard, and Judith Rapoport) were doing studies of childhood-onset OCD and observed that some of the children had an unusually abrupt onset of symptoms. Unlike typical cases of OCD, where symptoms begin gradually and may be hidden by the child for several weeks or months (because of their embarrassment over the irrational nature of the worries and behaviors), the children in the PANDAS subgroup reported a very sudden, dramatic symptom onset. The obsessive thoughts, compulsive behaviors, and motor or vocal tics appeared “overnight and out of the blue” and usually reached full-scale intensity within 24-48 hours.

The OCD and tic symptoms were accompanied by a variety of other neuropsychiatric symptoms, including separation anxiety, “anxiety attacks,” irritability, extreme mood swings, temper tantrums, and immature behaviors (like talking “baby talk”), hyperactivity, problems with attention and concentration, handwriting changes, and problems with math, reading and other school subjects. All of these ancillary symptoms were new (or much worse than baseline difficulties) and started at the same time as the OCD or tics, or very shortly thereafter. (See Reference #2 for a description of the first 50 PANDAS cases.)

The NIMH Investigators discovered that the OCD, tics, and other symptoms usually occurred in the aftermath of a strong stimulant to the immune system, such as a viral infection or bacterial infection. The first cases were given the name PITANDS for Pediatric Infection Triggered Autoimmune Neuropsychiatric Disorders. The first reported cases of PITANDS followed infections with influenza, varicella (chickenpox), and streptococcal bacteria (strep throat and scarlet fever). (See Reference #3 for descriptions of the PITANDS cases.) Later cases were reported to occur in association with Lyme disease and mycoplasma infections (“walking pneumonia”). The NIH investigators chose to focus on OCD symptoms that occurred after streptococcal infections (the PANDAS subgroup) because of a connection between OCD and Sydenham chorea, the neurological form of rheumatic fever.

Rheumatic fever is a collection of illnesses that occur as a result of untreated or partially treated streptococcal infections (primarily strep throat and scarlet fever). Rheumatic fever includes heart disease (“carditis”), joint disease (“arthritis”), skin abnormalities, and neurologic symptoms, known as Sydenham chorea or St. Vitus’ dance. Research studies suggest that rheumatic fever results from an untreated strep infection that triggers a pseudo-autoimmune reaction. The term “pseudo-autoimmune” is used to indicate the fact that the immune response isn’t really abnormal, but it causes harmful effects to the child because of cross-reactivity between the anti-strep response and the child’s own tissues.

The strep bacteria is a very ancient organism which survives in its human host by hiding from the immune system as long as possible. It does this by putting molecules on its cell wall that look nearly identical to molecules found on the child’s heart, joints, skin and brain tissues. This is called “molecular mimicry” and allows the strep bacteria to evade detection for a time. However, the molecules on the strep bacteria are eventually recognized as foreign to the body and the child’s immune system reacts to them by producing antibodies. Because of the molecular mimicry, the antibodies react not only with the strep molecules, but also with the human host molecules that were mimicked.

The cross-reactive antibodies then trigger an immune reaction that “attacks” the mimicked molecules in the child’s heart and causes carditis, or tissues in the brain (particularly the basal ganglia) and causes Sydenham chorea. Studies at the NIMH and elsewhere showed that some cross-reactive “anti-brain” antibodies don’t produce full-blown Sydenham chorea, but instead cause OCD, tics, and the other neuropsychiatric symptoms of PANDAS. (See Reference #4 for a discussion of the relationship between Sydenham chorea and PANDAS.)

Recognizing and Diagnosing Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

The diagnosis of PANDAS is a clinical diagnosis, which means that it depends on a carefully taken history and a physical examination, rather than on laboratory tests. The history must reveal an abrupt onset of OCD and/or tics (or sudden, dramatic worsening if the child had mild OCD or tics previously). The physical examination must rule out Sydenham chorea and other types of rheumatic fever, since they require different treatments. Laboratory tests can be useful in documenting that the child currently has a strep infection (which should be treated promptly!) or that they have had one recently. However, the laboratory tests cannot make a diagnosis – they can only reveal whether or not there has been a preceding strep infection (which may or may not be related to the current symptoms).

The criteria used to diagnose PANDAS are as follows:

1) Presence of clinically significant obsessions, compulsions and/or tics

2) Unusually abrupt onset of symptoms or a relapsing-remitting course of symptom severity.

During both the initial onset and subsequent recurrences, symptoms “explode” in severity overnight, reaching maximal impairment in 24 to 48 hours. Between episodes, symptoms usually decrease significantly and occasionally resolve completely. The following figure illustrates this episodic course:

3) Prepubertal onset

Note: This criterion is an arbitrary one, chosen because post-streptococcal reactions are rare after age 12. This criterion allowed NIMH to study a more homogeneous group of patients, but the investigators recognize that PANDAS could occur (rarely) among adolescents.

4) Association with other neuropsychiatric symptoms

The original PANDAS criteria specified that the associated symptoms were hyperactivity (ADHD) or other motor symptoms, but experience has shown that the list is longer. Various combinations of neuropsychiatric symptoms occur, such as OCD + tics + ADHD-like symptoms; or OCD + severe separation anxiety + bedwetting; or OCD + tics + hyperactivity + developmental regression. The possible combinations are too numerous to list, but in all cases, the associated symptoms should begin at the same time as the OCD (or within 1 – 2 days) and have an equally dramatic, sudden onset. The most common accompanying symptoms are:

a. Severe separation anxiety (e.g., child can't leave parent's side or needs to sleep on floor next to parent's bed, etc.)

b. Generalized anxiety. which may progress to episodes of panic and a "terror-stricken look"

c. Motoric hyperactivity, abnormal movements, and a sense of restlessness

d. Sensory abnormalities, including hyper-sensitivity to light or sounds, distortions of visual perceptions, and occasionally, visual or auditory hallucinations

e. Concentration difficulties, and loss of academic abilities, particularly in math and visual-spatial areas

f. Increased urinary frequency and a new onset of bed-wetting

g. Irritability (sometimes with aggression) and emotional lability. Abrupt onset of depression can also occur, with or without thoughts about suicide.

h. Developmental regression, including temper tantrums, "baby talk" and handwriting deterioration (also related to motor symptoms)

5) Association with streptococcal infection.

At initial onset, the symptoms may have followed an asymptomatic (and therefore untreated) streptococcal infection by several months or longer, so the inciting strep infection may have gone unnoticed. However, on subsequent infection recurrences, the worsening of the neuropsychiatric symptoms may be the first sign of an occult ("hidden") strep infection. Prompt treatment of the strep infection is often effective in reducing the OCD and other neuropsychiatric symptoms.

Strep throat infections can only be diagnosed by obtaining a throat culture that yields Group A beta-hemolytic streptococcal bacteria. In order to have a reliable throat culture, the swab must reach the oropharynx (the top back part of the throat) which typically is slightly uncomfortable and makes the child gag. A throat culture swab that only touches the back of the tongue will give a falsely negative result, as will one that is just touched to the sides of the throat. Poorly done throat cultures are a common cause of false negative results. Rapid strep tests can also give falsely negative results, as they miss about 10-15% of cases of strep throat. If the rapid strep test is negative, an overnight culture should be done to make sure that there aren’t strep bacteria present.

Anti-streptococcal titers can also be used to diagnose a strep throat, but require that two separate blood tests are done several weeks apart and timed just right to show a “rising titer.” Strep infections trigger the production of anti-streptococcal antibodies, which are measured by the titers. When the child is initially infected with the strep bacteria, his titers will be low, but should increase over the next 4-6 weeks as more anti-streptococcal antibodies are produced. If the child’s blood is tested too late, the titers may already be elevated, but it won’t be possible to know if these “high titers” are related to the current difficulties, or if they’re left over from a previous strep infection, since titers can remain elevated for several months or longer. Thus, a single “high anti-streptococcal antibody titer” isn’t sufficient to prove that a strep infection was the trigger for the child’s symptoms.

Recognizing and Diagnosing Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)

Because it is often difficult to demonstrate the relationship between strep infections and OCD/tic symptoms in PANDAS, clinicians and researchers met at NIH in July 2010 to discuss changes to the diagnostic criteria that would facilitate more rapid diagnosis and treatment of affected children. The meeting participants agreed that attention should be focused on the unique features of the children’s clinical presentation, rather than on the role that strep infections might play. To accomplish this goal, the PANDAS criteria were modified to describe PANS – Pediatric Acute-onset Neuropsychiatric Syndrome. PANS encompasses the whole group of acute-onset cases of OCD while PANDAS describes those cases of PANS that have a documented association with streptococcal infections. PANS and PANDAS are comparable to cancer and leukemia (respectively) as PANS is the large class of disorders and PANDAS is one specific type. The diagnosis of PANS is made entirely on the basis of the history and physical examination.

The diagnostic criteria for PANS are as follows:

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:

  1. Anxiety (particularly, separation anxiety)
  2. Emotional lability (extreme mood swings) and/or depression
  3. Irritability, aggression and/or severely oppositional behaviors
  4. Behavioral (developmental) regression (examples, talking baby talk, throwing temper tantrums, etc)
  5. Deterioration in school performance
  6. Sensory or motor abnormalities
  7. Somatic signs and symptoms, including sleep disturbances, bedwetting or increased urinary frequency.

3) Symptoms are not better explained by a known neurologic or medical disorder, such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others.
NOTE: 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 might include MRI scan, lumbar puncture or electroencephalogram (EEG) in some cases. More often, laboratory studies will be warranted and should include tests to determine if there is a current infection or ongoing immunologic dysfunction.

Treatment of PANS/PANDAS

Since PANS is newly described, research is ongoing to determine which interventions will be effective. If the diagnostic work-up of PANS reveals an infectious trigger, treatment of the infection may be useful in reducing symptom severity of the OCD and other neuropsychiatric symptoms. The following treatment information is directed at PANDAS, since that is where the research has been done, but may prove useful for PANS, as well.

Symptomatic Treatment

Children with PANDAS-related obsessive-compulsive symptoms will benefit from cognitive behavioral therapy (CBT) and/or anti-obsessional medications. Studies show that the best results are produced from the combination of CBT and an SSRI medication (such as fluoxetine, fluvoxamine, sertaline, or paroxetine). Children with PANDAS appear to be unusually sensitive to the side-effects of SSRIs and other medications, so it is important to “START LOW AND GO SLOW!” when using these medications. Clinicians should prescribe a very small starting dose of the medication and increase it slowly enough that the child experiences as few side-effects as possible. If symptoms worsen, the dosage should be decreased promptly. However, SSRIs and other medications should not be stopped abruptly, as that could also cause difficulties.

Treatment with Antibiotics

The best treatment for acute episodes of PANDAS is to eradicate the strep infection causing the symptoms (if it is still present). A throat culture should be done to document the presence of strep bacteria in the throat (oropharynx). If the throat culture is positive, a single course of antibiotics will usually get rid of the strep infection and allow the PANDAS symptoms to subside. Amoxicillin, penicillin, azithromycin, and cephalosporins are examples of antibiotics commonly used to treat strep infections. Toothbrushes should be sterilized or replaced during/following the antibiotics treatment, to make sure that the child isn’t re-infected with strep. It might also be helpful to check throat cultures on the child’s family members to make sure that none are “strep carriers” who could serve as a source of strep bacteria.

If a properly obtained throat culture is negative, the clinician should make sure that the child doesn’t have an occult strep infection, such as a sinus infection (often caused by strep bacteria) or strep bacteria infecting the anus, vagina, or urethral opening of the penis. Although the latter infections are rare, they have been reported to trigger PANDAS symptoms in some patients and can be particularly problematic, because they will linger for longer periods of time and continue to provoke the production of cross-reactive antibodies. The strep bacteria can be harder to eradicate in the sinuses and other sites, so the course of antibiotic treatment may need to be longer than that used for strep throat.

Some clinicians have advocated using antibiotics to treat acute symptoms of PANDAS, even when no strep infection can be found. They have observed significant improvement in the OCD and other neuropsychiatric symptoms following treatment with amoxicillin, azithromycin, and particularly with augmentin and other beta-lactam antibiotics. These case reports need to be confirmed by a controlled treatment trial before we can recommend use of antibiotics in the treatment of PANDAS.

A separate study conducted at NIMH suggests that the benefits of plasma exchange (plasmapheresis) and IVIG are specific to PANDAS-related symptoms. A group of children with non-PANDAS obsessive-compulsive symptoms had no improvement when treated with plasmapheresis using the same protocol that had been used so successfully for the PANDAS patients. Thus, the immune-based therapies should be used only in cases where it is clear that the neuropsychiatric symptoms are related to an autoimmune response (as in PANDAS and many cases of PANS). In addition to ensuring that the child’s symptoms fully meet the PANS or PANDAS criteria, the clinician may utilize laboratory tests to confirm the immune dysfunction. Among others, such testing might include anti-streptococcal antibody titers, anti-nuclear antibody titers, and a test of immune reactivity, such as an erythrocyte sedimentation rate (ESR) or C-reactive protein.

There is some disagreement about the utility of corticosteroids (like prednisone) in the treatment of PANDAS. Clinicians have reported improvement of OCD severity in conjunction with administration of steroids. However, there are also reports of steroids causing tics to worsen. Another difficulty with treating PANDAS patients with steroids is that they can only be used for a short period of time (to avoid serious long-term complications). Symptoms may have improved during the steroid administration, but will return after the steroids are stopped, often rebounding to a level that’s even worse than before treatment was started. For this reason, steroids are not routinely recommended in the treatment of PANDAS. However, they may help the child’s physician decide if IVIG or plasmapheresis treatment will be helpful, since a “steroid response” is a good indicator that the immune-based therapies will be of benefit.

Prevention of Future Episodes of PANDAS

To avoid future episodes of PANDAS, it may be helpful to use antibiotics as prophylaxis (prevention) against strep infections. Prophylactic antibiotics have proven to be quite beneficial to patients with rheumatic fever and Sydenham chorea. Two small clinical trials of prophylactic antibiotics in PANDAS showed that when antibiotics were effective in preventing strep infections, they also reduced the rate of recurrent episodes of PANDAS. The graph below shows the differences in symptomatic months for children receiving penicillin (PCN) and azithromycin (ZITH). The red line indicates the start of antibiotics prophylaxis, so marks to the left of the line represents the year prior to receiving antibiotics (most children were symptomatic for at least several months during the year) and the area to the right of the line shows the symptomatic months while taking penicillin or azithromycin.

It is important to note that the number of patients studied at NIMH is too small to provide definitive support for the use of prophylactic antibiotics in PANDAS. Thus, clinicians must decide whether they are appropriate for their patients, based on consideration of the known risks of antibiotic administration (potential for allergic reactions, secondary yeast infections, etc.) as well as the potential benefits of preventing strep infections. If the decision is made to use prophylactic antibiotics, clinicians should follow the guidelines established for rheumatic fever patients.


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