Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

27 Aug Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

Understanding PANDAS: When Childhood Infections Trigger Neuropsychiatric Disorders

Imagine waking up one day to find your child suddenly gripped by overwhelming fears, obsessive thoughts, or uncontrollable tics. What if these alarming changes came out of nowhere, seemingly overnight? For some families, this unsettling scenario is a reality, tied to a little-known condition known as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections—PANDAS. 

What is PANDAS?

PANDAS is a condition where a simple streptococcal infection—like the common strep throat—triggers a cascade of neuropsychiatric symptoms in children. First identified in the late 1990s, PANDAS belongs to a broader category called Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). The hallmark of PANDAS is the abrupt onset of obsessive-compulsive disorder (OCD) and/or tic disorders, which can appear almost overnight after a strep infection.

Recognizing the Symptoms

Children with PANDAS often experience a dramatic onset of OCD and/or tics, accompanied by a range of other symptoms like anxiety, irritability, emotional swings, aggression, and even behavioral regression. Parents may also notice sudden changes in motor skills, sleep disturbances, and unusual sensory sensitivities. These symptoms tend to flare up rapidly and can be incredibly distressing for both the child and their family. To diagnose PANDAS, children must exhibit at least two of the following symptoms within these categories:

A. Anxiety;

B. Emotional instability and/or depression;

C. Irritability, aggression, and/or extreme oppositional behavior;

D. Behavioral regression;

E. Decline in school performance;

F. Sensory or motor issues, such as increased sensitivity to sensory stimuli, hallucinations, dysgraphia, complex motor or vocal tics; and

G. Physical symptoms, including sleep disturbances, bedwetting, or frequent urination.

What causes PANDAS?

The underlying cause of PANDAS involves an autoimmune response gone awry. When the body fights off a streptococcal infection, it mistakenly targets the basal ganglia, a part of the brain that regulates movement and behavior. This immune attack leads to inflammation and dysfunction, manifesting in the neuropsychiatric symptoms associated with PANDAS.

Research points to molecular mimicry—a process where the immune system’s antibodies, initially intended to attack the strep bacteria, also mistakenly attack similar-looking proteins in the brain. If the blood-brain barrier is compromised during an infection, these antibodies can reach the brain and trigger the symptoms of PANDAS.

The Role of Immune Dysregulation in PANDAS 

Recent research highlights the significance of immune system dysregulation in PANDAS. The condition is believed to be an autoimmune encephalitis, where the immune system, in its attempt to fight off a streptococcal infection, inadvertently targets brain cells. This immune attack is thought to involve antibodies that mistakenly recognize the basal ganglia—a region of the brain involved in motor control and behavior—as a threat. The result is inflammation and a host of neuropsychiatric symptoms, including sudden-onset OCD, tics, and other behavioral changes.

New Findings on Neuroinflammation and Autoimmunity 

The understanding of PANDAS is evolving as researchers explore the complex interactions between infection, autoimmunity, and neuroinflammation. Studies have shown that children with PANDAS often have elevated levels of inflammatory markers in their blood, suggesting that systemic inflammation might play a role in the development and progression of the disorder. Additionally, imaging studies have identified abnormalities in the basal ganglia of affected children, further supporting the link between immune-mediated brain inflammation and the symptoms of PANDAS.

These insights underscore the importance of early intervention and a multidisciplinary treatment approach that addresses both the infection and the resulting immune dysregulation. By managing inflammation and supporting the immune system, healthcare providers can help mitigate the severity of symptoms and improve the long-term prognosis for children with PANDAS.

Diagnosing PANDAS: A Controversial Journey

Diagnosing PANDAS can be challenging and remains a topic of debate within the medical community. Unlike other conditions, PANDAS lacks a definitive lab test, making diagnosis reliant on clinical criteria, patient history, and evidence of a recent strep infection. Doctors often look for a sudden onset of OCD or tics, a history of strep infection, and neurological abnormalities to make a diagnosis.

However, some experts caution that PANDAS may be over-diagnosed, with symptoms possibly overlapping with other neuropsychiatric disorders such as Sydenham chorea, Tourette syndrome, or non-PANDAS-related OCD. This diagnostic gray area emphasizes the importance of a thorough evaluation by a knowledgeable healthcare provider. 

Treatment: A Multi-Pronged Approach

Managing PANDAS requires a comprehensive strategy tailored to the child’s specific needs. Treatment often includes:

1. Antibiotic Therapy: To address the underlying strep infection, antibiotics like penicillin or azithromycin are commonly prescribed. In some cases, prophylactic antibiotics may be used to prevent recurrence and subsequent symptom flare-ups.
2. Immunomodulatory Treatments: For children experiencing severe symptoms or not responding to antibiotics, therapies such as corticosteroids, intravenous immunoglobulin (IVIG), or plasmapheresis may be explored. These options are designed to decrease inflammation and regulate the immune system. Additional treatments might involve low-dose naltrexone (LDN), optimizing immune-supporting nutrients like vitamin D3 and zinc, or using specialized antihistamines such as Ketotifen.
3. Psychiatric and Behavioral Support: Cognitive-behavioral therapy (CBT), particularly exposure and response prevention (ERP), is highly effective for managing OCD symptoms. In some cases, medications like selective serotonin reuptake inhibitors (SSRIs) are also prescribed to manage anxiety and depression.
4. Supportive Care: Given the emotional toll PANDAS can take on both the child and their family, supportive care is crucial. This might include family counseling, educational accommodations, and therapies to address any motor or speech issues.

The Road Ahead: Prognosis and Long-Term Outcomes

The prognosis for children with PANDAS varies widely. Some may experience a full recovery, while others might have a relapsing-remitting course, with symptom flare-ups triggered by new strep infections. Early diagnosis and intervention are key to improving outcomes.

Although long-term studies are limited, current evidence suggests that many children improve significantly over time, especially with appropriate treatment. However, some may continue to experience symptoms into adolescence or adulthood, underscoring the importance of ongoing care and monitoring.

Building Healthy Foundations for Children with PANDAS

Supporting a child with PANDAS involves more than just medical treatment—it’s about creating a nurturing environment that promotes both physical and emotional well-being. Parents, caregivers, and educators play a vital role in recognizing early signs of symptom flare-ups and ensuring that children receive the necessary care.

Maintaining a healthy lifestyle is also essential. A balanced diet, regular exercise, and adequate sleep can help strengthen the immune system and support overall health. Reducing exposure to potential triggers, such as new strep infections, is crucial to managing the condition effectively.

By combining targeted medical treatments with emotional support and healthy living practices, children with PANDAS can achieve a better quality of life and minimize the impact of this disorder on their development.

References

Chang, K., Frankovich, J., Cooperstock, M., Cunningham, M. W., Latimer, M. E., Murphy, T. K., Pasternack, M., Swedo, S. E., Williams, K., Walter, J., & Gerardi, D. (2015). Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): Recommendations from the 2013 PANS consensus conference. Journal of Child and Adolescent Psychopharmacology, 25(1), 3-13.

Frankovich, J., Swedo, S., Murphy, T., Dale, R. C., Agalliu, D., & Williams, K. (2017). Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part II—use of immunomodulatory therapies. Journal of Child and Adolescent Psychopharmacology, 27(7), 574-593.

Murphy, T. K., Gerardi, D. M., Leckman, J. F., & Swedo, S. E. (2010). Pediatric acute-onset neuropsychiatric syndrome. Psychiatric Clinics of North America, 33(3), 591-610.

Prato, A., Gulisano, M., Scerbo, M., Barone, R., Vicario, C. M., & Rizzo, R. (2020). Diagnostic approach to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): A narrative review of literature data. Frontiers in Pediatrics, 8, Article 575566.

Snider, L. A., Lougee, L., Slattery, M., Grant, P., & Swedo, S. E. (2005). Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biological Psychiatry, 57(7), 788-792.

Swedo, S. E., Leonard, H. L., Garvey, M., Mittleman, B., Allen, A. J., Perlmutter, S., Lougee, L., Dow, S., Zamkoff, J., & Dubbert, B. K. (1998). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases. The American Journal of Psychiatry, 155(2), 264-271.

Thienemann, M., Murphy, T., Leckman, J., Shaw, R., Williams, K., Kapphahn, C., Frankovich, J., Geller, D., Bernstein, G. A., & Chang, K. (2017). Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part I—psychiatric and behavioral interventions. Journal of Child and Adolescent Psychopharmacology, 27(7), 566-573.