PANS/PANDAS – Symptoms, Diagnosis, Treatment, & New Research

The discovery and development of PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome) and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) is very interesting. The identification of the condition(s) began with observations made by researchers and clinicians in the late 1990s.

The initial recognition of PANDAS arose from clinical observations by Dr. Susan Swedo and her colleagues at the National Institute of Mental Health (NIMH) in the United States. They observed a subgroup of children who experienced sudden and severe onset of neuropsychiatric symptoms following infections, particularly streptococcal infections like strep throat.

Swedo and her team began to document and study cases of children who exhibited symptoms such as obsessive-compulsive disorder (OCD), tic disorders (such as Tourette syndrome), anxiety, emotional instability, and behavioral regression following streptococcal infections. They noticed that these symptoms appeared to have an acute and abrupt onset, distinct from the gradual onset typically seen in these disorders.

Through their research, Swedo and her colleagues identified commonalities among these cases, such as the temporal relationship between the onset of neuropsychiatric symptoms and the occurrence of streptococcal infections. They also noted other features, including prepubertal onset, episodic course of symptoms, and association with other infections or environmental triggers.

Based on their observations and findings, Swedo and her team proposed diagnostic criteria for PANDAS in 1998. These criteria included the abrupt onset of OCD or tic disorders, prepubertal onset, episodic course of symptoms, association with streptococcal infection, and other neuropsychiatric symptoms. These criteria were intended to help clinicians identify and diagnose cases of PANDAS.

Over time, researchers and clinicians have continued to investigate the relationship between infections, immune dysregulation, and neuropsychiatric symptoms in children. The concept of PANS was later introduced in 2010 to encompass a broader range of triggers beyond streptococcal infections, reflecting the growing understanding of the complexity of these conditions.

The symptoms of PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) can vary widely from one individual to another. However, there are some common symptoms that are often associated with these disorders:

Symptoms typically appear suddenly, often following an infection in the case of PANDAS or other triggers in the case of PANS. Obsessive thoughts and compulsive behaviors are a hallmark feature of both PANS and PANDAS. These obsessions and compulsions can be intrusive and disruptive to daily life. Motor and vocal tics, which are sudden, repetitive movements or vocalizations, may occur in some cases. These can include eye blinking, throat clearing, or repetitive movements of the limbs.

Additional symptoms may include anxiety, including panic attacks, separation anxiety, and generalized anxiety. Mood swings, irritability, and aggression may occur.

Insomnia, difficulty falling asleep, frequent waking during the night, or other sleep disturbances are also common. Heightened sensitivity to sensory stimuli such as light, sound, touch, or taste may be present. Some individuals may experience changes in motor coordination or fine motor skills.

Other symptoms related to PANS/PANDAS include difficulty concentrating, memory problems, and cognitive deficits.

It’s important to note that not all individuals with PANS or PANDAS will experience all of these symptoms, and the severity and combination of symptoms can vary widely. Additionally, symptoms can fluctuate over time, with periods of exacerbation and remission.

Diagnosing PANS/PANDAS can be challenging and typically involves a comprehensive evaluation by a healthcare professional experienced in pediatric neuropsychiatric disorders. There is no single definitive test for these conditions, so diagnosis relies on careful consideration of the individual’s medical history, symptoms, and other factors.

Generally, the physician will take a detailed medical history, including information about the onset and progression of symptoms, any recent illnesses or infections, family history of neuropsychiatric disorders, and any past treatments or interventions. A thorough physical examination will be conducted to assess the individual’s overall health and to look for any signs of infection or other medical conditions. The physician will also assess the individual’s neuropsychiatric symptoms, including the presence of obsessive-compulsive behaviors, tics, anxiety, mood disturbances, cognitive changes, and other relevant symptoms.

While there is no specific laboratory test for PANS or PANDAS, certain tests may be ordered to help rule out other potential causes of the symptoms. These may include blood tests to check for signs of infection, inflammation, autoimmune disorders, and other relevant markers. In some cases, the evaluation may involve collaboration with specialists such as pediatric neurologists, infectious disease specialists, immunologists, or psychiatrists with expertise in neuropsychiatric disorders.

It’s important to note that diagnosing PANS or PANDAS can be complex, and the process may vary depending on the individual case.

The treatment for PANS/PANDAS typically involves a multidisciplinary approach aimed at addressing the underlying triggers, reducing inflammation, and managing neuropsychiatric symptoms. This may involve treating infections (such as streptococcal infections or other pathogens), addressing environmental triggers, and managing other medical conditions that may contribute to symptoms.

Since inflammation is believed to play a role in PANS and PANDAS, anti-inflammatory treatments may be considered. This can include nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids to reduce inflammation and alleviate symptoms.

Immunomodulatory therapies may be prescribed to modulate the immune response and reduce autoimmune activity. This can include therapies such as intravenous immunoglobulin (IVIG) or plasma exchange (plasmapheresis) to help regulate the immune system.

Sometimes, medications commonly used to manage neuropsychiatric symptoms associated with PANS and PANDAS include selective serotonin reuptake inhibitors (SSRIs) for anxiety and OCD symptoms, antipsychotic medications for severe behavioral disturbances, and alpha agonists for tic disorders.

Cognitive Behavioral Therapy and other forms of psychotherapy may be beneficial in helping children and adolescents with PANS and PANDAS learn coping strategies, manage anxiety, and address maladaptive thoughts and behaviors associated with neuropsychiatric symptoms.

Providing supportive care and interventions to address the child’s needs, including educational accommodations, occupational therapy, and speech therapy, can be important components of treatment. Support from family, teachers, and other caregivers is also essential.

Implementing lifestyle modifications such as maintaining a healthy diet, ensuring adequate sleep, and reducing stressors can help support overall well-being and may complement other treatment strategies.

It’s important to note that the treatment approach for PANS and PANDAS is individualized based on the specific needs and circumstances of each child. Collaboration among pediatricians, neurologists, psychiatrists, immunologists, and other healthcare professionals is often necessary to provide comprehensive care. Additionally, ongoing monitoring and adjustment of treatment may be needed to address changes in symptoms and response to therapy.

In late January 2024 a very interesting publication appeared in the Journal of Personalized Medicine. A group of physicians/researchers identified folate receptor autoantibodies in a large number of children with PANS/PANDAS. Now, why is this pertinent? Folate receptor autoantibodies (FRAAs) hinder the transport of folate (vitamin B9), especially into the brain and CSF (cerebrospinal fluid). And, folate, a water-soluble vitamin, is integral for cerebral metabolism and function throughout development and adolescence.

Essentially, folate receptor autoantibodies caused a dysfunction of the folate receptor alpha (FRɑ), the main transporter of folate into the brain. In healthy conditions, folate binds to the FRɑ, which then undergoes endocytosis to actively transport folate across the blood–brain barrier. This cannot happen in the presence of folate receptor autoantibodies.

Two FRAAs have been described (blocking and binding FRAAs). The blocking FRAA binds specifically to the site where folate binds to the FRα, thereby preventing folate from binding to the FRɑ, while the binding FRAA binds to other regions of the FRɑ and interferes with its ability to function optimally.

Folate receptor autoantibodies are diagnosed through the use of the FRAT^® test. This simple blood test identifies both blocking and binding autoantibodies.

FRAT^® was conducted on 47 children and adolescents clinically diagnosed with PANS/ PANDAS to determine the presence of folate receptor autoantibodies. Astonishingly, 63.8% of these patients were found to have folate receptor autoantibodies. This prevalence was strikingly similar to that found in ASD. Patients with CFD and/or ASD positive for FRAAs respond well to leucovorin, a folate that can circumvent the blocking of the folate receptor alpha. With this in mind, physicians believed that the same type of treatment may be beneficial for PANS/PANDAS patients.

In the same publication, the authors provided a case study of one patient who showed significant improvement in OCD and anxiety with leucovorin. Additionally, they go on to state that other PANS/PANDAS patients also did very well when treated with leucovorin or 5-methyltetrahydrofolate (5-MTHF). This is all very promising and exciting information for PANS/PANDAS patients, indeed!

As with any medical condition, please consult your physician for information and guidance.