What is PANDAS?

Jul 29

Has your child suddenly developed neurological problems following a sore throat or Streptococcus infection? Have they developed any symptoms such as obsessions, compulsions, hard to control urges and spontaneous movements or vocalizations? Have they demonstrated symptoms such as anxiety, bedwetting, emotional meltdowns, or other neurologic issues? They could be experiencing a syndrome called Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, or PANDAS.

How Common is PANDAS?

PANDAS typically presents in children between the ages of 3 and puberty. The PANDAS Network estimates that 1 out of every 200 children is currently living with PANDAS.

What Causes PANDAS?

PANDAS is an autoimmune neurologic disorder that occurs after a Streptococcus A infection, usually manifesting as case of strep throat. This results in an autoimmune response known as cross-reactivity, in which the immune system misidentifies proteins in the child’s own nervous system as part of the infection. This causes the immune system to attack cells in an important modulation system called the basal ganglia. It manifests as an often sudden and severe impairment in emotional and behavioral regulation (6).

What are the Symptoms of PANDAS?

Symptoms include obsessive compulsive or repetitive behaviors, fear, panic attacks, separation anxiety, irritability, mood changes, screaming outbursts, developmental regression, visual or auditory hallucinations, depression, and suicidal thoughts. These symptoms can range from mild to severely debilitating. Often the first sign of PANDAS is sudden onset obsessive thoughts and compulsive behaviors.

The onset of the symptoms is approximately four to six weeks after a streptococcal infection and includes behaviors similar to the obsessive-compulsive disorder (OCD) and Tourette's syndrome. Symptoms can interfere with school and social behavior, and can rapidly become debilitating.

The psychological symptoms of PANDAS include repetitive, obsessive-compulsive behaviors, separation anxiety, fear, and panic attacks, incessant screaming, irritability, frequent mood changes, emotional and developmental regression, visual or auditory hallucinations, depression and suicidal thoughts.

Physical symptoms of PANDAS may include tics and uncommon movements, sensitivity to light, sound and touch, deterioration of motor skills such as handwriting, hyperactivity or the inability to concentrate, memory problems, sleep disorders, refusal to eat which may lead to weight loss, joint pain, frequent urination and bed wetting, and seeming to be in a catatonic state.

Symptoms can be rapidly progressive, and usually reach a maximum within 2-3 days, unlike other childhood psychiatric diseases that develop gradually (6).

How is PANDAS Diagnosed?

The current consensus criteria for a diagnosis of PANDAS are as follows:

I. Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake
II. Concurrent presence of additional neuropsychiatric symptoms, (with similarly severe and acute onset), from at least two of the following seven categories:
- 1. Anxiety
- 2. Emotional lability and/or depression
- 3. Irritability, aggression, and/or severely oppositional behaviors
- 4. Behavioral (developmental) regression
- 5. Deterioration in school performance (related to attention-deficit/hyperactivity disorder [ADHD]-like symptoms, memory deficits, cognitive changes)
- 6. Sensory or motor abnormalities
- 7. Somatic signs and symptoms, including sleep disturbances, enuresis, or urinary frequency
III. Symptoms are not better explained by a known neurologic or medical disorder, such as SC (7).

How Does PANDAS Affect the Brain?

To understand the effects of PANDAS we must first understand the basics of the immune system.

The brain contains immune cells known as microglia. In normal circumstances, microglia function to help take out the brain’s trash, by removing damaged neurons and cleaning out cellular debris. They also function to provide a local response to cellular injury and infection. They are essentially the “first responders” in the central nervous system.

Chronic or excessive activation of microglia may in turn cause neuronal damage through the release of potentially cytotoxic molecules such as proinflammatory cytokines, reactive oxygen intermediates, proteinases and complement proteins. In PANDAS, microglial cells become overactive, which leads to significant neurological tissue damage.

B-lymphocytes are another important class of immune cells. B-cells produce antibodies, which are tags that attach to proteins that the immune system wants to destroy. Antibodies make it easier for cytotoxic T-cells and natural killer cells to identify pathogens they need to attack.

Antibodies are a mechanism that allows the immune system to remember certain pathogens so we don’t get sick from a specific infection more than once. Once we have resolved an infection and produced antibodies, our immune system already has the “recipe” to beat the pathogen if we were to encounter it a second time.

Baj et al (1) did a research review and compiled some very interesting data. They reported from other studies that those with PANDAS had enlarged striatum on imaging, and high amounts of antibodies in this area. The striatum is a part of the basal ganglia network, which is important for modulation of behavior, emotions, cognition, and movement. The tics, obsessions, movement disorders, and behavioral meltdowns seen in PANDAS are the result of the immune system attacking the basal ganglionic system and causing it to function abnormally. Another study by Pavone et al (2) found that almost 2/3rds of children with PANDAS were found to have antibodies to the basal ganglia.

With more and more evidence emerging about how the brain, immune system, and the gastrointestinal tract all working together, we also want to look at the gut when considering PANDAS. A study by Quagliariello et al (3) found that streptococcal infections alter gut bacterial communities, leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. They found younger patients with PANDAS had altered ratios of gut bacteria compared to healthy control subjects, as well as more inflammation and reduced activity of GI pathways known to be involved in brain neurotransmitter function.

How is PANDAS Usually Treated?

Therapy for PANDAS begins with antibiotics to treat the Streptococcus infection. Unfortunately, by the time that PANDAS has been identified the Strep infection is only a small part of the problem. Aggressive therapy to stop the autoimmune response is critical in early stages. This generally involves the use of steroid medications. For more severe cases, often the only effective treatment to stop the autoimmune attack on the basal ganglia network requires intravenous infusion of IVIG.

Once the immune system has been stabilized, psychopharmacology is the primary treatment for PANDAS. Psychiatric medications may range from selective serotonin reuptake inhibitors to control OCD symptoms, to antipsychotics to regulate behavioral outbursts have all been employed in PANDS treatment. While these may prove helpful, all have potential side effects and contraindications (17).

There are a number of noninvasive therapies that have shown some benefit in addressing the symptoms of PANDAS. Dutta and Cavanna (4) studied positive benefits of habit reversal therapy, which is a technique where the child learns to perform behavior opposite of their tic when they feel the onset of the urge. This process recruits modulation centers in the frontal lobe, leading to improved top-down inhibition of unwanted behaviors. The therapy also encourages a positive collaboration between the child and the provider. The child becomes empowered by the choice to resist what they saw as a previously unstoppable tic.

A case study by Guido et al (5) showed that a child with PANDAS who underwent an 8-session program of eye movement desensitization and reprocessing therapy (EMDR) demonstrated a significant reduction in OCD symptoms. This is encouraging because EMDR is a noninvasive therapy that works by improving brain modulation through exercises that involve the eyes, frontal lobe, and basal ganglia.

How is the NeuroRescue Program Different?

Successful PANDAS treatment must always begin with management of the autoimmune condition. Before any form of neurorehabilitation can be effective, we must first ensure that there is no active immune attack on the nervous system. This may take the form of metabolic and immune testing to determine and deal with any triggers that may be worsening the autoimmune response. It may require identifying and treating food and chemical sensitivities, or dealing with other occult infections. In cases of an active autoimmune attack, treatment may require cotreatment with other providers for medication management. Usually this will involve prescriptions for steroids, or in severe cases, IVIG infusions.

Once the immune response has been stabilized, we can work to improve the function of the impacted neurological pathways. Dysfunction in the basal ganglia, frontostriatal circuits, and the limbic system can produce the tics and OCD seen in PANDAS. When we activate these areas with targeted therapies and exercises, and couple this with stimulating other brain regions that fire into the basal ganglia, we can often improve the function and integrity of these systems. No two cases of PANDAS are alike, and all of them require unique and specific rehabilitation protocols to rejuvenate the damaged pathways and systems.

The brain’s frontostriatal circuit is of critical importance in PANDAS and other tic disorders. This is a pathway involving the frontal lobe and the basal ganglia. Collectively they form one of the brain’s primary inhibitory systems. They work to suppress unwanted behavior and involuntary responses such as tics and other outbursts. Their function is impaired in PANDAS, and although the pathophysiology is different, the impact on basal ganglia function is very similar to what is seen in obsessive-compulsive disorder, tic disorders, and Tourette syndrome. Rehabilitation strategies for these other basal ganglia disorders can often be very helpful in decreasing the symptoms of PANDAS.

Research shows that the basal ganglia become increasingly activated during the suppression of tics. As test subjects increased in age, greater activation was seen in the dorsolateral prefrontal cortex, a specific aspect of the frontal lobe that functions in response inhibition (8).

When our dopamine system is dysfunctional, our ability to inhibit unwanted responses is decreased. The ability to ignore the shiny object, the “squirrel” moment, or in this case, the urge, is reduced. The parts of the frontal lobes and basal ganglia involved in response inhibition are also directly involved in the production of specific classes of eye movements. We use advanced neurodiagnostic technologies to measure the function of these inhibitory systems. We can not only use these types of eye movements to measure the level of dysfunction in these pathways, but can also use them as a means to rehabilitate the system.

We have our patients perform Videonystagmography testing (also known as VNG), wherein we precisely measure a host of different eye movements with infrared tracking, and compare their results to those from normal subjects. One important eye movement that requires a great deal of inhibitory control is a saccade, which is a fast jump of the eyes from target to target. A prosaccade is when you quickly jump your eyes to a target. An anti-saccade involves jumping the eyes away from a presented target. Anti-saccades are harder to perform, as they require inhibiting the reflex that tries to make the eyes jump towards the newly presented target. Anti-saccades involve a conscious choice to move the eyes in the opposite direction, which requires high-level executive function. Anti-saccades are produced directly from the dorsolateral prefrontal cortex, the important modulation center for response inhibition that becomes more active as the brain matures. We routinely use anti-saccade exercises in treating our PANDAS and tic disorder patients, in order to activate the dorsolateral prefrontal cortex and enhance its ability to inhibit tics.

Jeter et al (9) studied prosaccades, anti-saccades, and saccades to remembered targets, which requires spatial memory in addition to eye movement accuracy. They found that tic disorder patients had more frequent errors on their prosaccades, slower reaction time on anti-saccades, and had higher error rates on memory saccades.

Jung et al (10) studied saccades and anti-saccades with tic disorder patients. They found that when provided an easy task of performing saccades to targets, Tourette patients had worse reaction times and velocity of movements compared with normal subjects. When saccades and anti-saccades were combined in the same test, the Tourette subjects performed BETTER than everyone else. They were worse at easier tasks than control subjects, but better at the harder tasks than control subjects. This implies that when someone living with Tourette syndrome has more challenging work to do, they perform better than they do with less stimulating, repetitive tasks. It also implies that by activating the dorsolateral prefrontal cortex, their ability to modulate their tics and unwanted behavior is greatly enhanced.

Anti-saccade therapies are extremely effective, but are only one of myriad ways to activate the brain’s inhibitory networks. We use a wide variety of technologies and therapies to help build function in these pathways to help bring tics under control. These include rhythmic entrainment therapies to build modulation within the basal ganglia network. Motor timing has been shown to be impaired in children with Tourette syndrome and other associated basal ganglia disorders (12). We use a therapy system called the Interactive Metronome to rehabilitate these systems, which has been shown to be very effective in such cases (13).

Another secondary issue seen in people with basal ganglia disorders is decreased balance and postural stability. Children with Tourette syndrome have been compared to healthy children under a variety of postural stability challenges. The Tourette syndrome children showed greater deficits in maintaining stable upright posture, especially when undergoing challenges to their sensory systems (11). Deficits in posture increases a person’s fall risk, and therefore increases their risk of sustaining concussion. Vestibular rehabilitation becomes very necessary for these individuals, including those suffering from PANDAS.

There are a series of reflexes that we are all born with, called primitive reflexes. These help the brain develop, by creating specific motor patterns in response to sensory input. These reflexes are normal in infants, but should be all fully attenuated by the first birthday. There are direct associations with neurodevelopmental conditions and retained primitive reflexes. Children with Tourette syndrome often demonstrate a series of retained primitive reflexes. Exercises to attenuate primitive reflexes have been shown to be very helpful in a wide variety of neurodevelopmental disorders (14).

Non-invasive neurostimulation techniques have shown good promise in resolving Tourette syndrome and associated tic disorders. Transcutaneous direct current simulation (tDCS) is one such therapy, which involves a safe, gentle electrical current applied to the scalp. This helps improve function and integration between frontal and basal ganglia pathways, and has shown to be effective in reducing tics (15).

Another advanced technology shown to help people living with basal ganglia disorders is transcranial magnetic stimulation (TMS). This involves an MRI-strength magnet with a focused beam of magnetic energy applied to the forehead. It stimulates the dorsolateral prefrontal cortex directly through the skull. As we have already seen, the DLPFC is a primary center involved in executive function and inhibitory control. TMS therapy can produce significant improvement in behavioral modulation, including the suppression of tics (16). We reserve tDCS and TMS therapy for individuals over the age of 18, however it is not uncommon for the effects of PANDAS to persist well into adulthood.

Every NeuroRescue Program is different, with your therapies chosen based on your diagnostic testing and the realities of your condition. It is impossible to take a cookie-cutter approach to the treatment of a condition as complex as PANDAS. No two brains are alike, and nor are any of our NeuroRescue Programs.

How Does the NeuroRescue Program Work?

We design your unique NeuroRescue Program to be among the most comprehensive diagnostic and therapeutic protocols available today. We create individual NeuroRescue Programs based on a comprehensive analysis of every relevant neurological system and pathway, using gold-standard, cutting edge neurodiagnostic technologies and examination procedures and state-of-the-art therapies.

We begin with your Discovery Day, wherein we perform a comprehensive history and neurological examination. This allows us to identify the areas and pathways of your child’s brain that have been impacted by PANDAS. We do this by precisely quantifying the function of their visual, vestibular, and proprioceptive systems through computerized analysis of eye movements, inner ear reflexes, and balance in a host of different sensory conditions.

We employ technologies including Videooculography and Saccadometry to measure several classes of eye movements. We use Video Head Impulse Testing to measure the function of the inner ear, and Computerized Dynamic Posturography to assess how the eyes and inner ear work with the motor system to balance in different sensory conditions.

We use NeuroSensoryMotor Integration testing to evaluate hand-eye coordination and cognition, and Virtualis testing to assess dynamic eye tracking and perception of vertical in a virtual reality environment.

We combine all of this with a comprehensive physical and neurological examination of your child’s sensory, motor, autonomic, and cognitive systems. We review any relevant laboratory testing, radiological imaging, and prior neurodiagnostic testing, and integrate that information with our findings.

We use this information to identify which parts of your child’s nervous system are working properly, which systems are struggling, and the precise point at which their systems fatigue.

We can then design a NeuroRescue Program that is unique and specific to your child’s brain, and theirs alone. The NeuroRescue Program works to rejuvenate and reintegrate the damaged neurons and pathways in their central nervous system. It works to improve energy, endurance, and functional capacity within their involved fragile systems.

We use our technologies and procedures to not only see what we need to address, but also when it is time to stop and let your child rest. We address their impaired neurological function from multiple angles of therapy, and provide metabolic support to improve neurological recovery.

While we cannot bring back neurons that have been lost to PANDAS, the NeuroRescue Program allows us to take the pathways that remain and maximize their efficiency and endurance. And by focusing on the integration of systems, we can do more than just get pathways working better, we can get them working together again. This gives us our best opportunity to return your child to living a healthy, vibrant, and fulfilling life.

Your Next Best Step:

Living with PANDAS can be challenging, but there is hope for functional recovery. To see if the NeuroRescue Program is right for you, contact one of our patient care coordinators to schedule your Discovery Day.

And remember, it’s never too late to start getting better.