PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome)

Published on November 30, 2025 at 4:56 PM

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) are immune-mediated neuropsychiatric disorders characterized by the abrupt onset of obsessive-compulsive behaviors, tics, and mood or anxiety disturbances. In PANDAS, the condition is triggered by Group A Streptococcus infections, whereas PANS can be precipitated by a broader range of infectious, inflammatory, or autoimmune events. Although historically described in children, emerging evidence suggests that adult-onset PANDAS/PANS may occur, likely due to lingering or reactivated autoimmune responses. Estimated prevalence in children is low, with PANDAS affecting roughly 0.2–1% of school-aged children, though exact rates are difficult to determine due to underdiagnosis and overlapping conditions. The underlying pathophysiology involves autoantibodies that cross-react with basal ganglia proteins (e.g., dopamine D1/D2 receptors, lysoganglioside GM1, and tubulin), triggering microglial activation, dopaminergic dysregulation, and disruption of cortico-striatal-thalamo-cortical circuits, which collectively produce the hallmark neuropsychiatric symptoms.

In PANDAS, infection with Group A Streptococcus (GAS) triggers the production of antibodies against bacterial antigens, especially M-proteins. Due to structural similarity with human neural proteins, these antibodies cross-react with host neurons, particularly in the basal ganglia. In PANS, similar mechanisms may occur following viral infections, other bacteria, or systemic autoimmune triggers.

 

Different proteins can be targeted by the immune system and, because each protein has a different function, means there are different types of PANDAS/PANS with different symptoms. It is important to note that more than one protein can be impact, so individuals may present as one or more type.

 

Anti-DRD1 (Dopamine D1 receptor)

The Dopamine D1 receptor (DRD1) is a protein in the brain that helps nerve cells communicate and is important for motivation, reward, attention, and controlling emotions. DRD1 is especially active in areas like the striatum, nucleus accumbens, and parts of the frontal and limbic brain, which control things like goal-directed behavior, feeling pleasure, and managing stress. In some cases of PANDAS or PANS, the immune system mistakenly attacks DRD1 with antibodies. This can suddenly disrupt these brain circuits and cause symptoms that look like obsessive-compulsive disorder, anxiety, depression, or ADHD. People with this subtype may experience sudden compulsive behaviors (like repeating tasks or checking things), trouble feeling motivated or enjoying activities, racing thoughts, irritability, being easily upset, difficulty handling stress, and trouble focusing or making decisions. Because these symptoms appear suddenly and can change quickly, they are often confusing and can be misdiagnosed as a purely psychiatric condition.

 

Anti-DRD2 (Dopamine D2 receptor)

The Dopamine D2 receptor (DRD2) is a protein in the brain that helps control movement, coordination, and habit formation. It is especially active in areas like the caudate, putamen, globus pallidus, and substantia nigra, which are part of the basal ganglia, the brain’s main movement and habit center. In some cases of PANDAS or PANS, the immune system mistakenly attacks DRD2 with antibodies. This can suddenly disrupt these brain circuits and cause symptoms that may look like tics, movement disorders, or sudden behavioral changes. People with this subtype may experience involuntary movements such as blinking, facial grimacing, shoulder shrugging, or jerking of the arms and legs, sudden onset of compulsive behaviors, irritability, mood swings, trouble controlling impulses, and difficulty coordinating movements. Because these symptoms appear quickly and can change from day to day, they are often misdiagnosed as Tourette syndrome, ADHD, or other movement or psychiatric disorders.

 

Anti-lysoganglioside GM1

Lysoganglioside GM1 is a molecule found on the surface of many brain cells, especially in areas that control movement, coordination, sensory processing, and emotional regulation. In some cases of PANDAS or PANS, the immune system mistakenly produces antibodies against GM1, which can disrupt how brain cells communicate. People with this subtype may experience problems with movement and coordination, such as tremors, muscle twitching, stiffness, or clumsiness, as well as sudden changes in mood, irritability, heightened sensitivity to sounds, lights, or touch, and anxiety. They may also notice difficulty concentrating, feeling “wired but tired,” or trouble starting and completing tasks. Because the symptoms can appear quickly and affect both physical and emotional control, they are sometimes misdiagnosed as ADHD, sensory processing disorder, anxiety, or other movement or psychiatric conditions.

Anti-tubulin
Tubulin is a protein inside brain cells that acts like the cell’s “skeleton,” helping maintain structure, support communication between cells, and coordinate movement and thinking. In some cases of PANDAS or PANS, the immune system mistakenly attacks tubulin with antibodies, which can interfere with how brain cells send messages and stay connected. People with this subtype may experience problems with coordination and movement, such as clumsiness, muscle stiffness, or difficulty controlling fine motor skills, along with cognitive challenges like brain fog, forgetfulness, trouble concentrating, or difficulty organizing thoughts. Emotional changes can also occur, including irritability, mood swings, and feeling emotionally “flat” or numb. Because these symptoms affect both thinking and movement, they are sometimes misdiagnosed as ADHD, learning disorders, depression, or anxiety.

Skip to the end for antibody- specific treatment.

 

Antibody Subtype Main Symptoms Common Misdiagnoses
Anti-DRD1 Sudden compulsive behaviors (OCD) Trouble feeling motivated or enjoying activities Racing thoughts Irritability Emotional outbursts Trouble focusing Difficulty coping with stress OCD Depression Anxiety ADHD
Anti-DRD2 Sudden tics or jerky movements (blinking, grimacing, shoulder shrugging) Compulsive behaviors Irritability Mood swings Trouble controlling impulses Difficulty with coordination Tourette syndrome ADHD Movement disorders OCD
Anti-lysoganglioside GM1 Tremors Muscle twitching Stiffness Clumsiness Heightened sensitivity to lights, sounds, or touch Anxiety Trouble concentrating Feeling “wired but tired” ADHD Sensory processing disorder Anxiety Movement disorders
Anti-tubulin Clumsiness Muscle stiffness Difficulty with fine motor skills Brain fog Forgetfulness Trouble organizing thoughts Irritability Mood swings Emotional flattening ADHD Learning disorders Depression Anxiety

Phases of PANDAS

PANDAS symptoms are phase-dependent, reflecting the immune/neurochemical state of the basal ganglia, limbic system, and cortical loops. There are four PANDAS stages:

 

Acute PANDAS Flare (Immune and Microglia Activation) Phase

  • This is the “sudden and severe” phase. Symptoms peak quickly (hours todays) and often follow strep exposure.

Chronic Neuroinflammation / Recovery Phase

  • Symptoms are less severe than acute flare, more variable, and often improve with rest, sleep, or anti-inflammatory interventions. This phase can last weeks to months.

Sensory Hypersensitivity and Anxiety Phase

  • This phase is often triggered by minor infections or stress, and sensory processing is the dominant symptom.

OCD / Tics / Basal Ganglia Involvement Phase

  • This phase represents the classic “basal ganglia-targeted” PANDAS symptoms, often what clinicians first notice when evaluating for diagnosis.

Treatment Methodologies

Treatments that remove or neutralize the autoantibodies

These are the most direct ways to restore dopamine receptor signaling.

IVIG

  • Reduces autoantibody production
  • Neutralizes pathogenic antibodies
  • Downregulates B-cell activity
  • Shown in studies to restore basal ganglia DRD2 receptor signaling in PANDAS
  • Often produces rapid reduction in OCD/tics

Plasmapheresis (PEX)

  • Physically removes circulating autoantibodies
  • Considered the most direct immune reset
  • Clinically, one of the strongest symptomatic responders, especially for severe tics/OCD

Steroids (oral or IV methylprednisolone)

  • Reduce inflammation in the basal ganglia
  • Temporarily dampen autoantibody production
  • Improve dopamine receptor signaling by reducing cytokine interference

 

Treatments that improve dopamine signaling

These don’t remove the antibodies, but compensate for impaired DRD2 signaling.

Dopamine stabilizers

  • Aripiprazole (Abilify)
    • Partial agonist at DRD2
    • Can bridge impaired DRD2 signaling
    • Sometimes helps emotional regulation or tics
  • Low-dose risperidone
    • DRD2 antagonist
    • Counterintuitively can help stabilize dopamine output
    • Most useful for aggression or severe OCD, but not ideal long-term in PANDAS due to receptor blockade

Nutraceuticals that support dopamine synthesis

These help restore baseline dopamine tone so that remaining functional DRD2 receptors can still work.

  • Tyrosine (dopamine precursor)

  • Vitamin B6 (P5P)- cofactor for converting L-DOPA to dopamine

  • Iron- essential for tyrosine hydroxylase

  • Methylfolate and Methylcobalamin- support BH4 synthesis, required for dopamine production

  • SAMe- supports methylation of catecholamines

 

Treatments that target microglial activation & basal ganglia inflammation

Strongest class for PANDAS/PANS-like neuroinflammation.

These directly calm overactive microglia, which are central to PANDAS symptoms.

Low-dose naltrexone (LDN)           <---------------------------------------------Dr. Katelin's Pick

  • Potent microglial modulator
  • Reduces neuroinflammation
  • Often improves:
    • emotional lability
    • sensory issues
    • pain sensitivity
  • Can indirectly restore DRD2 receptor responsiveness

NSAIDs           <---------------------------------------------Dr. Katelin's Pick

  • Ibuprofen or naproxen
  • Reduce basal ganglia inflammation for improved dopamine signaling

Omega-3 fatty acids (DHA-heavy)           <---------------------------------------------Dr. Katelin's Pick

  • Reduce neuroinflammation
  • Improve membrane fluidity, which improves receptor function
  • May indirectly support DRD2 responsiveness

Curcumin, luteolin, quercetin

  • Mast-cell stabilizers
  • Reduce cytokines that interfere with dopamine pathways
  • Support recovery of receptor sensitivity

Scutellaria baicalensis — Baicalin           <---------------------------------------------Dr. Katelin's Pick

  • Inhibits TLR4, NF-κB, and NLRP3 inflammasome
  • Reduces IL-6, TNF-α
  • Protects dopamine neurons
  • Crosses BBB easily
  • Often improves: 
    • anxiety
    • OCD
    • panic
    • neuroinflammatory flares

Luteolin

  • Mast cell and microglial dual inhibitor
  • Blocks IL-6, IL-1β, TNF-α
  • Stabilizes mast cells which reduces peripheral immune triggers
  • Used clinically in many PANS protocols (e.g., NeuroProtek)
  • Often improves:
    • sensory hypersensitivity
    • iritability
    • ADHD-like symptoms

Curcumin (with black pepper or nanoparticle forms)

  • Blocks microglia and NF-κB
  • Improves dopamine signaling
  • Reduces oxidative stress and glutamate excitotoxicity
  • Helps basal ganglia inflammation
  • Often improves:
    • OCD
    • tics
    • limbic overactivation

Resveratrol

  • Currently under debate as to if humans can get to an clinically effective dose.
  • Inhibits microglia via SIRT1
  • Reduces IL-6, TNF-α
  • Protects BBB integrity
  • Used for:
    • neuroprotection
    • reducing neuroinflammatory fatigue

Cytokine-Lowering / Autoimmune-Modulating Herbs

These modulate immune signaling rather than blunt it, which is ideal for CNS autoimmune cases.

Ashwagandha

  • Reduces IL-6, TNF-α

  • Balances cortisol which reduces neuroinflammatory priming
  • Normalizes GABA/dopamine tone
  • Better for chronic states than acute flares

Reishi (Ganoderma lucidum)

  • Immune regulatory (not suppressive)
  • Reduces IL-1β, IL-6, and TNF-α
  • Stabilizes the Th1/Th2 balance
  • Calms limbic hyperactivation
  • Often improves:
    • autoimmune-driven anxiety
    • nightmares
    • sleep disruption

Astragalus

  • Strengthens immune surveillance without overactivation
  • Reduces inflammatory cytokines
  • Protects BBB endothelial cells
  • More for chronic immune rebuilding after PANDAS flares

Mast-cell stabilizers

Important because MC activation worsens neuroinflammation. Many PANDAS kids also have mast cell activation and histamine intolerance, which worsen neuroinflammation.

Quercetin

  • Very strong mast-cell stabilizer
  • Anti-microglial
  • Lowers oxidative stress and glutamate
  • Reduces blood–brain barrier permeability
  • Often improves:
    • sensory issues
    • irritability
    • panic
    • sleep problems

Nigella sativa (Black Seed)           <---------------------------------------------Dr. Katelin's Pick

  • Reduces IL-6, TNF-α
  • Calms mast cells
  • Enhances GABA function
  • Reduces neuroinflammatory headaches
  • Good for anxiety plus inflammation combination types

Dopaminergic pathway protectors

These protect basal ganglia circuits under autoimmune attack.

Ginkgo biloba

  • Anti-inflammatory in basal ganglia
  • Improves dopamine signaling
  • Reduces microglia activation
  • Enhances blood flow to PFC & basal ganglia
  • Often improves:
    • tics
    • OCD loops
    • cognitive fog

Rhodiola rosea

  • Modulates microglia
  • Lowers IL-6
  • Stabilizes dopamine & serotonin under stress
  • Helps “wired but tired” states
  • Not ideal during severe agitation or mania-like energy spikes

BBB-protective / Neuroregenerative herbs

These restore or protect the blood–brain barrier, which is often compromised in PANDAS flares.

Gotu Kola (Centella asiatica)

  • Repairs endothelial tight junctions
  • Reduces microglial activation
  • Stimulates BDNF (neuroplasticity)
  • Anti-IL-6 and anti-TNF-α
  • Useful during recovery phases, not acute crisis

Lion’s Mane (Hericium erinaceus)           <---------------------------------------------Dr. Katelin's Pick

  • Reduces neuroinflammation
  • Supports nerve growth factor (NGF)
  • Improves cognitive recovery
  • Avoid in active flares if mast-cell activation is high- can aggravate some

Herbal Combinations That Work Best for Neuroinflammation

Treatments Designed for Specific Phases of PANDAS/PANS

For acute PANDAS flare (immune plus microglia):

  • Luteolin
  • Baicalin
  • Curcumin
  • Quercetin

For chronic neuroinflammation or recovery:

  • Gotu Kola
  • Resveratrol
  • Reishi
  • Lion’s Mane

For sensory hypersensitivity plus anxiety:

  • Luteolin
  • Quercetin
  • Ginkgo biloba

For OCD/tics/basal ganglia involvement:

  • Curcumin
  • Baicalin
  • Ginkgo biloba

The Strongest CNS-Immune Regulators

The top core herbs, based on both research and clinical patterns in neuroimmune disorders.

1. Baicalin (Scutellaria)
2. Luteolin
3. Curcumin
4. Quercetin
5. Resveratrol
6. Ginkgo

Antibody- Specific Treatment

Anti-DRD1 (Motivation, reward, and emotional regulation)

  • Goal: Support dopamine D1 signaling, reduce limbic hyperactivation, and calm microglia.
  • Treatments:
    • Herbs: Baicalin (Scutellaria), Luteolin, Curcumin, Ginkgo biloba
    • Nutrients: Tyrosine (dopamine precursor), B vitamins (especially B6, folate, riboflavin), magnesium
    • Lifestyle / Behavioral: Cognitive-behavioral therapy for sudden-onset OCD/anxiety, structured routines to improve motivation, reward-based reinforcement
    • Focus: Emotional regulation, motivation, and OCD-type behaviors

Anti-DRD2 (Motor circuits, tics, compulsions)

  • Goal: Protect nigrostriatal dopamine signaling, reduce basal ganglia inflammation, and support motor control.
  • Treatments:
    • Herbs: Baicalin (Scutellaria), Curcumin, Ginkgo biloba, Luteolin
    • Nutrients: Tyrosine, magnesium, zinc, omega-3 fatty acids (anti-inflammatory)
    • Lifestyle / Behavioral: Habit-reversal therapy for tics, gentle physical activity to maintain coordination
    • Focus: Motor control, tics, compulsive behaviors

Anti-lysoganglioside GM1 (Sensory, motor, and emotional dysregulation)

  • Goal: Reduce basal ganglia inflammation, stabilize sensory processing, calm limbic hyperactivation.
  • Treatments:
    • Herbs: Baicalin (Scutellaria), Luteolin, Quercetin (mast cell stabilization), Resveratrol
    • Nutrients: Omega-3 fatty acids, magnesium, vitamin D, antioxidants
    • Lifestyle / Behavioral: Sensory integration techniques, mindfulness for anxiety, structured environments to reduce sensory overload
    • Focus: Sensory sensitivity, anxiety, motor control

Anti-tubulin (Motor coordination plus cognitive / emotional dysregulation)

  • Goal: Support neuronal structure, improve connectivity, reduce neuroinflammation.
  • Treatments:
    • Herbs: Baicalin (Scutellaria), Lion’s Mane (nerve growth), Gotu Kola (BBB repair, microglial modulation), Resveratrol
    • Nutrients: B vitamins (B12, folate, riboflavin), magnesium, omega-3 fatty acids, antioxidants
    • Lifestyle / Behavioral: Cognitive exercises for executive function, fine motor training, structured daily routines
    • Focus: Cognitive clarity, coordination, emotional stabilization

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