Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

PANDAS is defined as the acute, dramatic childhood onset of obsessive-compulsive disorder (OCD) and/or tic disorders following a recent group A $β$ -hemolytic streptococcal (GABHS) infection.
The condition is currently considered a specific infectious subtype under the broader umbrella diagnosis of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), which includes all cases of acute-onset OCD or tics regardless of the triggering infectious agent.
A diagnosis of PANDAS should not be assigned to children who have preexisting OCD or tics that merely worsen during an illness, as infections and systemic stress are universally known to exacerbate baseline tic and compulsive behaviors.

The pathogenesis of PANDAS is rooted in an immune-mediated, postinfectious autoimmune response targeting the brain.
Following a GABHS infection (such as streptococcal pharyngitis), the host mounts an immune response that generates cross-reactive autoantibodies.
These autoantibodies inadvertently target and bind to the basal ganglia, triggering localized neuroinflammation.
This inflammation disrupts normal signaling within the corticostriatal-thalamocortical motor and behavioral pathways, directly resulting in the acute onset of complex movement disorders and severe neuropsychiatric symptoms.

The hallmark clinical feature is an explosive, sudden onset (often overnight) of severe OCD symptoms, restrictive food intake, or motor/vocal tics.
The symptom severity typically peaks rapidly within 2 to 3 days of onset.
The primary symptoms are almost always accompanied by a constellation of severe secondary neuropsychiatric deficits:

Clinical Domain	Associated Signs and Symptoms
Psychiatric and Behavioral	Severe separation anxiety; acute personality changes; oppositional behaviors; intense emotional lability; depression; aggression; and nighttime fears or nightmares.
Neurologic and Motor	Chorea-like movements; soft neurologic signs such as resting tremors; and coordination difficulties.
Cognitive and Academic	Acute behavioral or developmental regression; sudden deterioration in school performance; specific deterioration in math skills; and dysgraphia (deterioration of handwriting).

PANDAS remains a controversial clinical diagnosis because specific autoantibodies directed against basal ganglia cells have not been consistently isolated in routine laboratory assays.
A thorough diagnostic workup is required to rule out other known medical and neurologic disorders that mimic acute psychosis or movement disorders, including Sydenham chorea, Tourette syndrome, systemic lupus erythematosus, and autoimmune encephalitis.
Establishing the diagnosis requires proving a temporal association between the symptom onset and a recent GABHS infection.
Checking single antistreptococcal antibody titers (e.g., antistreptolysin O and anti-deoxyribonuclease B) has no diagnostic utility, as most children naturally develop positive titers by their teenage years.
A recent, active infection is best confirmed by demonstrating a doubling of streptococcal antibody titers in paired samples drawn weeks apart.
A positive rapid throat culture alone only confirms that the child is a carrier of the Streptococcus species; it does not confirm a recent invasive infection causing the neurologic symptoms.
Children presenting with sudden psychiatric symptoms without encephalitic features (e.g., altered consciousness, seizures) generally do not require extensive neurodiagnostics beyond streptococcal testing, whereas patients with atypical focal neurologic signs or delirium require magnetic resonance imaging (MRI), electroencephalogram (EEG), lumbar puncture, and cerebrospinal fluid (CSF) analysis.

Comprehensive management of PANDAS involves three primary realms of treatment: psychotherapeutic, antimicrobial, and immunomodulatory.
Psychiatric Interventions: Because behavioral therapies require time to take effect, symptomatic psychiatric interventions must begin expeditiously. Cognitive-behavioral therapy (CBT), combined with selective serotonin reuptake inhibitors (SSRIs), is the standard of care for providing relief from severe OCD and anxiety symptoms.
Antimicrobial Therapy: Positive streptococcal cultures or antibody titers are not an indication for antibiotic therapy unless the patient is physically ill with an active infection. However, when an active infection is proven, a full course of appropriate antibiotics is utilized to eliminate the underlying source of neuroinflammation. There is currently insufficient data to support the use of long-term prophylactic antibiotics.
Immunomodulatory Therapy: In severe cases, immunomodulatory therapies are theoretically aimed at treating the underlying immune system disturbance. However, the use of corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange remains experimental, controversial, and is generally not recommended in routine pediatric practice due to a lack of definitive evidence proving they alter the course of tics or OCD symptoms.