Research and awareness of PANDAS/PANS are crucial for preparing health care providers with the best medical knowledge to help patients and their families.
PANDAS is the acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. PANS is the acronym for Pediatric Acute Onset Neuropsychiatric Syndrome.
Both are associated with post-infectious basal ganglia encephalitis (BGE).
Recent studies have produced insights into the nature of autoimmune basal ganglia encephalitis.
New Columbia University research shows how the immune response to strep throat triggers the blood-brain barrier breakdown in post-infectious basal ganglia encephalitis (BGE). This highlights the need for early diagnosis and treatment for better outcomes in children affected by PANDAS/PANS.
Strep throat causes the body to initiate an immune response against the infection. Certain patients produce antibodies, called auto-antibodies, that also attack the individual’s healthy brain cells. Until recently, scientists did not have a full understanding of how these autoantibodies entered the brain. These new insights will likely lead to more options for testing and treating PANDAS/PANS.
Can strep throat cause autoimmune encephalitis?
Autoimmune encephalitis (AE) is a group of central nervous system autoimmune disorders that occur when the body’s immune system mistakenly attacks healthy brain tissue. Post-infectious BGE is a subset of AE resulting from viral, bacterial, or fungal infections.
PANDAS/PANS are types of BGE linked to infection, usually strep throat.
The basal ganglia are interconnected structures within the brain that regulate neural functions including cognitive and emotional response, motor movement, and habit learning. Patients with encephalitis of the basal ganglia region in the brain frequently have an abrupt onset of symptoms. In addition, some people may be genetically susceptible to autoimmunity, which may help explain why some develop BGE after infection, while others do not.
Research using mice produced much-needed information about how the cells triggered in the immune response travel and damage the brain. This evidence will help improve diagnosing, treating and managing BGE disorders like PANDAS/PANS.
What is the blood-brain barrier?
The blood-brain barrier is a highly selective, semi-permeable boundary of specialized cells—known as endothelial cells—that line the brain’s blood vessels. The blood-brain barrier protects the brain from infection by preventing molecules in the circulating blood from indiscriminately entering the brain.
Untreated strep throat can result in the production of these autoantibodies that target the brain. The infection produces a powerful cell response to fight the infection. This usually occurs in the throat, nose, and tonsils. Lymphocytes, or inflammatory cells, cause an inappropriate immune response that targets the patient’s healthy cells. Lymphocytes are commonly present in many autoimmune diseases.
How do bacteria pass through the blood-brain barrier?
Recurrent strep throat leads to the accumulation of lymphocytes in the mucous membrane, upper nasal cavity, and surrounding tissue. Clinical research suggests that the cell response from T helper 17 (Th17) lymphocytes plays a critical role in transporting autoantibodies across the blood-brain barrier.
The Th17 lymphocytes may travel along the odor-sensing olfactory nerves to the brain. Once in the brain, the lymphocytes release inflammatory cytokine proteins necessary for immune cell communication. The cytokines from the lymphocytes then stimulate specialized immune cells of the central nervous system, called microglia, to release more inflammatory cytokines. The inflammatory cytokines released by the lymphocytes and microglia cells trigger the breakdown of the blood-brain barrier, which allows toxins and pathogens to enter the brain.
Inflammatory cytokines released by Th17 lymphocytes and microglia cells trigger the breakdown of the blood-brain barrier by:
- Damaging tight junction (TJ) proteins. TJ proteins join endothelial cells of the blood-brain barrier to prevent the transport of molecules from the blood to the brain.
- Increasing endothelial transcytosis, or the transport of molecules. In endothelial transcytosis, molecules are transported within endothelial cells and into the brain.
This combination of factors allows autoantibodies circulating in the blood to enter the brain, where they can cause damage.
Does strep throat cause neurological problems?
Children with PANDAS/PANS often present with neurological and behavioral symptoms. This may result from the immune cell response in an untreated strep throat infection.
The Th17 lymphocytes are essential in transporting autoantibodies across the blood-brain barrier. Once the lymphocytes enter the brain, they begin to interfere with neuronal function. This process can result in the onset of neurological and psychiatric symptoms associated with PANDAS/PAN and other BGE disorders.
Can basal ganglia damage be reversed?
New research is currently being conducted to examine the role of these lymphocytes in humans suffering from post-infectious BGE disorders. Eventually, studies in humans may increase options for the diagnosis of children with PANDAS/PANS.
There is no definitive test for PANDAS/PANS. Currently, these disorders are diagnosed based on clinical symptoms and the presence of strep A infection or autoantibodies against cytokine proteins in the brain. Understanding how to stop and treat the breakdown of the blood-brain barrier is essential to providing better support and care to families affected by these diseases.
Early identification of BGE cases is critical to improving treatment and management in patients. Early treatment is critical to reducing permanent complications from the disease. Knowledge of PANDAS/PANS is constantly advancing with new diagnostic and treatment options, and more research to better understand these disorders.