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If you are desperately trying to figure out why your child went from straight-A student, star athlete, independent, and fully functional to having OCD, separation anxiety, behavioral regression, verbal or motor tics, becoming completely dysfunctional essentially overnight, this article may hold the answers for helping your child regain their normal life again!

PANS & PANDAS are two similar conditions related to neuropsychiatric changes in children, due to toxic and infectious triggers. PANS stands for Pediatric Acute Neuropsychiatric Syndrome, while PANDAS stands for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Strep. One of the main differences between PANS & PANDAS is that the etiology for PANDAS has been established as Group A Streptococcal (GAS) infections since the 1990s. PANS, which was only coined in 2012 (1), denotes PANDAS-like cases where strep could not be implicated as the cause of symptoms, and often another causal microbe or toxin was detected, such as Bartonella (2), Epstein-Barr virus, Mycoplasma Pneumoniae, Lyme disease (though less often), Varicella Zoster (aka chickenpox), Influenza A, and even the common cold (3). There can even be environmental triggers in PANS/PANDAS such as mold exposure, chemicals, or heavy metals.

While the etiology of both conditions differ, the clinical presentation generally manifests identically. Typically, healthy and normally functioning children experience a rapid decrease in appropriate behavior, transforming virtually overnight, within several days or weeks. The hallmarks of PANS/PANDAS children is the acute onset of obsessive-compulsive disorder (OCD), separation anxiety, eating disorders (47%), verbal and motor tics (70%), involuntary body movements, sleep disorders (80%) behavioral regression like baby talk and tantrums (98%), rapid decline in academic performance, math skills and handwriting (90%), ADHD, inattentiveness, hyperactivity as well as severe mood swings, rage outbursts, aggression, urinary issues (90%) frequent urination, bed-wetting, sleep disorders (80%), sensory hypersensitivity or insensitivity (40%) hallucinations (10%) and even suicidal ideation in some extreme cases (4). Interestingly, research has found that PANS/PANDAS affects children differently by gender. Boys are 2.5 to 4.7 times more likely to develop PANS/PANDAS (5).

PANS/PANDAS are autoimmune conditions, meaning the body produces antibodies against a foreign invader but due to molecular mimicry, ends up mistaking its own tissues as the invader and attacks them. In the case of PANS/PANDAS, structures in the brain known as the basal ganglia or “gatekeepers” of the brain, are targeted and attacked, causing massive brain inflammation. The basal ganglia reside deep within the brain and are necessary to direct control of voluntary movements, emotions, eye movements, cognition, process-based learning, and habit learning. When the cells of the basal ganglia are constantly being attacked, it produces the somatic and neuropsychiatric manifestations of PANS/PANDAS. MRI studies have shown that children with PANDAS have neuroanatomical differences, specifically significantly larger basal ganglia structures, compared to healthy age-matched controls (6).
In the case of PANDAS, strep causes the autoimmune encephalitis response. If strep lingers for more than 3-5 days, the body creates antibodies against the microbes. However, because of molecular mimicry by the bacteria, the immune system reacts not only to the strep itself but also to the human host molecules that were mimicked and attacks host tissues. This is known as autoimmune “cross-reaction” (7).

Studies have been done in mice, where one group was purposely infected with strep and another group was then injected with strep antibodies. The results showed the development of identical OCD-like symptoms and behaviors, which appear to be linked to antibody deposits in the same brain areas (basal ganglia) that have been implicated in human studies (4). Thus, PANDAS is a post-strep disease, not caused by strep microbe itself but an immune response that can linger long after the infection is gone.

The psychiatric symptoms that develop as a result of PANDAS can be devastating. Children often act out at home or in school, become dysfunctional due to OCD behaviors like handwashing, picky eating due to believing the food is contamination, that they might choke, or vomit, and later body image issues, begin showing hoarding tendencies, do things they know they should not like having angry outbursts at siblings or hurting pets. When asked why they did it despite knowing better, they often answer “I don’t know, my brain told me to” or “I am a bad kid and I don’t know why!”. If a child is receiving everything they need to prosper including adequate nutrition, sleep, socialization, parenting, learning environment, and has not experienced overt trauma or neglect, they are not a “bad” or “spoiled” child, but likely suffering from brain inflammation!

While blood tests do exist to help determine if a child has PANS or PANDAS, the only officially accepted diagnosis for PANS/PANDAS is the fulfillment of the following criteria. There has been considerable controversy in the medical field over these diagnoses, but in 2012 the definition of PANDAS was expanded to include the presentation of the symptoms without the etiological factor being recognized as strep, now known as PANS (1).

There are many symptoms associated with PANS, but the criteria for diagnosis include (8):
-A sudden and acute onset of OCD and/or severely restricted food intake.
-Simultaneous presence of similarly acute and severe onset of other neuropsychiatric issues from at least two of the following categories:
-Emotional lability (severe mood swings, intense reactions, dramatic changes in opinions or feelings, depression to the point of suicidal ideation)
-Panic, generalized anxiety, separation anxiety
-Behavioral and/or developmental regression (suddenly acting much younger than their age, baby talk)
-Aggression, irritability, severely oppositional or defiant behavior
-New sensory or motor processing problems (sensitivity to light or noise, dramatic worsening in handwriting and drawing)
-Deteriorating in academic performance (loss of math skills, reading comprehension, ability to focus, hyperactivity, reprimanded for bad behavior)
-Somatic symptoms like frequent urination, bed-wetting, sleep disturbances
*The symptoms are not better explained by and cannot be attributed to known neurological issues, medical disorders such as Sydenham’s Chorea or Lupus, trauma, or other psychiatric phenomena.

The Criteria of PANDAS
Diagnosis’ are similar, with several notable differences. These include age restrictions, with onset between age 3 and onset of puberty for PANDAS diagnosis. This age restriction is not applicable to the diagnosis of PANS. Additionally, there must be evidence of strep being the underlying catalyst to symptom onset. Lab testing for strep will be explained below. While PANS/PANDAS are pediatric conditions, there has been little research done as to how it may present later into adulthood if untreated. There is some evidence that adult-onset OCD may be related to similar causes (9), but further research is warranted.

Determining that the diagnosis of the condition is in fact PANS/PANDAS and not another serious illness with similar symptoms is critical. Other conditions to rule out include Sydenham’s Chorea which causes involuntary jerking of the head and extremities, infectious or toxic encephalitis (versus autoimmune), tumor or stroke, toxins like medications, or illicit substances, or child abuse, particularly sexual abuse.

One of the main characteristics of PANS/PANDAS is that it’s behavior change and regression onset occurs very abruptly. This differs from psychiatric issues like OCD and eating disorders that develop gradually over time, which can have their own separate etiologies. PANS/PANDAS behavior can also be episodic (relapse-remit cycle), having good days and bad days, unlike conditions where these behaviors are consistent and constant. A child may have tics, OCD, or both without having PANDAS. Additionally, most school-aged children experience strep throat on average two to three times per year (7).

While most PANS/PANDAS cases develop immediately, within days or weeks, there is also a change that it can happen more gradually in the case of PANDAS, when a child receives antibiotics for a strep infection, which will knock down the concentration of strep microbes in the body. However, if the antibiotics did not fully eradicate the infection, it can rebound and cause the onset of PANDAS symptoms. This is also why giving a PANDAS child antibiotics may be helpful for short-term symptomatic relief, but the infection and resulting neuropsychiatric symptoms may come back with a vengeance. In these cases, we need to address the root cause of why the immune system is weak. Strep is the final trigger in PANDAS, but not the root cause, which we will discuss later.

Testing for PANS/PANDAS
While lab tests are not a diagnostic tool for PANS/PANDAS themselves, they can be helpful in terms of deciding on clinical treatments and protocols for the symptoms.
For PANDAS, strep can be tested through the throat or nasopharyngeal swabs and cultured for 48 hours to detect its presence. Blood antibody tests for strep include ASO, Anti-strep dNase B, and ACHO, however, there are many possibilities of false-positives and false-negatives with strep antibody testing. As PANDAS is a poststreptococcal condition, the antibodies cause the inflammation and autoimmune reaction, and not the strep microbes themselves.
The Cunningham panel measures 5 specific antibody levels and the antibodies’ capability to stimulate and trigger neurological symptoms. The higher the levels, the greater the likelihood that the patient’s psychiatric and neurologic behaviors are due to an infection. While this test is the gold standard, it does not qualify as a diagnostic tool and can be prohibitively expensive to run.

The Rey-Osterrieth complex figure test helps determine a child’s working memory capacity and visuo-spatial skills for copying. Using this test multiple times can help track if treatment is improving their condition or not. Interestingly, another commonly seen marker for visuo-spatial issues in PANS/PANDAS children is a “left margin drift” when they are writing on paper.
Antibiotics are traditionally the main conventional course of treatment in PANDAS. While they can provide relief and remission in some cases, as mentioned above, antibiotics are often just a band-aid and symptoms can rebound with a vengeance, as the root cause was not addressed. Intravenous immunoglobulin therapy is another popular treatment, however, in my clinical experience, it is again just a temporary band-aid. Plasmapheresis is another option but expensive and difficult to find. The blood is removed from the body and filtered to remove the antibodies, then returned to the body. And you guessed it, once again, this may be helpful for a time, but did not address the underlying cause!

For the psychiatric symptoms and in cases of PANS where they cannot find an infectious root, mental health professionals may simply try to mask the symptoms with psychotropic medications like SSRIs, benzodiazepines, anxiolytics, and antipsychotics.

Getting to the Root Cause
A holistic approach to addressing PANS and PANDAS includes eradicating the underlying infectious agent and reducing the immunological response that has been reported to cause the neuropsychiatric symptoms, through natural means like herbs, binders, and nutritional supplements. In some cases, the challenge lies in correctly identifying the specific infectious agent or toxic trigger.

Strep in PANDAS and the associated triggers in PANS are not necessarily the underlying root cause, but the final drop in the bucket, the proverbial straw that broke the camel's back. In almost all cases, the immune system has been previously weakened due to toxins, infections, or genetic susceptibilities, and couldn’t keep up with toxic/infectious burden, then autoimmunity was triggered by final pathogenic influence. A healthy immune system should be able to keep strep in check at all times. When I work with children to address PANS/PANDAS in my clinic, we aim to lower the toxic body burden by identifying and addressing underlying issues with parasites, bacteria, fungus, mold in the environment, heavy metals, chemicals, tick-borne illnesses, traumas, etc. to allow the immune system to regulate itself, regain proper function as it was designed to and do its job effectively!