ASPIRE board members Susan Swedo, MD, and Gabriella True, sit down to talk about PANDAS, PANS, and post-streptococcal autoimmune basal ganglia encephalitis, their disease mechanisms, recent research, its remitting and relapsing course, and more.
“Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection or PANDAS can also be called post-streptococcal autoimmune basal ganglia encephalitis. Like other forms of autoimmune encephalitis, PANDAS appears to be caused by aberrant antibodies that are initially produced to target the invading strep organisms but cross-react with components of neuronal cells in the caudate, putamen, and other crucial brain structures. The misdirected antibodies set off an inflammatory response that interferes with basal ganglia functions, producing a constellation of behavioral, psychiatric, and neurologic symptoms. Primary among these are obsessions, compulsions, and eating restrictions. These are often accompanied by extreme anxiety, depression, mood swings, behavioral regression, personality changes, and neurological symptoms, such as cognitive changes, sensory sensitivities, sleep difficulties, and urination problems (symptoms of PANS – Pediatric Acute-onset Neuropsychiatric Syndrome). For strep-triggered episodes, the symptoms may respond to antibiotic treatment of the underlying strep infection. In other cases, immunomodulatory therapies can reduce brain inflammation and restore the child to full health.” – Susan Swedo, MD
Gabriella: Is PANDAS a form of Autoimmune Encephalitis?
Dr. Swedo: Yes! PANDAS is autoimmune encephalitis of the basal ganglia (caudate, putamen, and other brain structures). Like other types of autoimmune encephalitis (AE), PANDAS is thought to arise from cross-reactive antibodies that set off an inflammatory response in the basal ganglia. The inflammation interferes with basal ganglia functions, leading to a variety of behavioral, psychiatric, and neurologic symptoms. PANDAS is unique in that it is known to be triggered by a specific infectious agent – Group A streptococci (the cause of “strep throat” and scarlet fever.) If detected early enough, PANDAS may respond to antibiotic treatment of the strep infection. In other cases, immunomodulatory therapies can reduce brain inflammation and restore the child to full health.
Gabriella: Does everyone with PANDAS have AE? If not, what do those with a milder presentation have?
Dr. Swedo: If a child meets all clinical criteria for PANDAS, they do have autoimmune encephalitis (AE), even if symptoms are mild. Basal ganglia autoimmune encephalitis (or autoimmune encephalitis of the basal ganglia) is another name for PANDAS. PANDAS is unique among AEs because the triggering organism is known to be Group A streptococcal bacteria. If strep bacteria are present (in the throat, perianal region, or other locations), they must be eradicated with antibiotic treatment before the child can begin to recover. In cases where PANDAS is caught early, antibiotics may be the only treatment needed. In other cases, the use of an immunomodulatory therapy (such as steroids or non-steroidal anti-inflammatory medications like ibuprofen or naproxen) will reduce brain inflammation and restore the child to full health.
Gabriella: Is PANS a form of AE or just possibly some of the other infectious trigger PANS? What if PANS is triggered by a metabolic issue or stress?
Dr. Swedo: PANS stands for Pediatric Acute-onset Neuropsychiatric Syndrome. As the name states, PANS is a syndrome, not a disorder or a disease. By definition, a syndrome is a collection of symptoms that occur together in a specific, recognizable pattern – there is no assumption made about etiology. Syndromes can be caused by a variety of factors, ranging from infections or metabolic disturbances to psychosocial stressors or traumas. Some cases of PANS will turn out to be manifestations of AE, but most will not.
Gabriella: How do Dr. Agalliu’s, Dr. Cunningham’s, and Dr. Pittenger’s studies bolster or prove that PANDAS is a form of AE?
Dr. Swedo: The findings from Columbia, Yale, and other institutions are providing evidence to support the hypothesized disease mechanism of PANDAS. PANDAS appears to result from cross-reactive antibodies that are initially produced against invading streptococcal bacteria but also react with components on human neurons. Essentially, the antibodies misrecognize brain tissue as foreign and set off an inflammatory immune response. Research by Dr. Cunningham in Oklahoma and, more recently, by Dr. Pittenger at Yale has shown that the cross-reactive antibodies are reacting with neuronal cells in the caudate, putamen, and other basal ganglia structures. The misdirected antibodies set off an inflammatory response that interferes with basal ganglia functions, producing a constellation of behavioral, psychiatric, and neurologic symptoms.
The role of Group A streptococcal (GAS) bacteria in PANDAS is being elucidated by Dr. Agalliu and his colleagues at Columbia University. They’ve shown that recurrent GAS infections produce neuroinflammation directly by activating inflammatory cells and indirectly by opening the blood-brain barrier to permit entry of the cross-reactive antibodies to the basal ganglia. Taken together, the recent studies provide ample evidence to prove that PANDAS is a GAS-triggered form of autoimmune encephalitis.
Gabriella: Can PANDAS be a form of AE since PANDAS is relapsing and remitting?
Dr. Swedo: The relapsing-remitting nature of PANDAS does not eliminate it as a form of autoimmune encephalitis (AE). The recurrence of PANDAS is entirely related to the fact that a single infection does not gain protective immunity with Group A streptococcal (GAS) bacteria. Each time a vulnerable child has another GAS infection, they may suffer a recurrence of their neuropsychiatric symptoms. Further, GAS infections provoke an immune response that quickly generalizes so that other infectious agents and non-infectious factors (such as psychosocial stressors) can also trigger a neuroinflammatory immune response.
Note that PANDAS is a form of Autoimmune Encephalitis with its unique cluster of symptoms; therefore, not every symptom often associated with other forms of AE are seen in PANDAS patients. Below is information on what AE is from the NIH Genetic & Rare Disease Information Center.
Autoimmune encephalitis refers to a group of conditions that occur when the body’s immune system mistakenly attacks healthy brain cells, leading to inflammation of the brain. People with autoimmune encephalitis may have various neurologic and/or psychiatric symptoms. Neurologic symptoms may include impaired memory and cognition, abnormal movements, seizures, and/or problems with balance, speech, or vision. Psychiatric symptoms may include psychosis, aggression, inappropriate sexual behaviors, panic attacks, compulsive behaviors, euphoria or fear. Symptoms may fluctuate, but often progress over days to a few weeks. Symptoms can progress to loss of consciousness or even coma.