Tests
1st tests to order
clinical diagnosis
Test
PANS is a diagnosis of exclusion and other causes for the neuropsychiatric symptoms, such as Sydenham chorea, systemic lupus erythematosus, or autoimmune encephalitis, should be ruled out at initial presentation.[1]
Result
features of PANS include acute onset (<72 hours) of obsessive-compulsive symptoms or severely restricted food intake, with similarly severe and acute onset of at least 2 concurrent cognitive, behavioral, or neurologic symptoms
throat culture for group A streptococcus (GAS)
Test
Take a vigorous throat swab from the patient and their close contacts (regardless of a complaint of sore throat), ideally near the time of symptom onset.[2][20][33]
A throat culture is recommended as it is the most sensitive (90% to 95%) and specific test for GAS.[2][20][64]
GAS is the most common preceding infection at onset and relapses.[3][4][7][9][35]
Result
positive for GAS infection
polymerase chain reaction (PCR) for group A streptococcus (GAS)
Test
Take a vigorous throat swab from the patient and their close contacts (regardless of a complaint of sore throat), ideally near the time of symptom onset.[2][20][33]
PCR testing has high sensitivity and specificity comparable to that for throat culture, but it is more expensive and less readily available than RADT for GAS.[65]
Result
positive for GAS infection
rapid antigen detection test (RADT) for group A streptococcus (GAS)
Test
Take a vigorous throat swab from the patient and their close contacts (regardless of a complaint of sore throat), ideally near the time of symptom onset.[2][20][33]
RADT for GAS, if available, offers the advantage of immediate point-of-care testing, but about 15% of GAS pharyngitis is missed with RADTs.[33] If the RADT is negative, follow up with a throat culture or polymerase chain reaction.[20][33][64]
Result
positive for GAS infection
antistreptococcal serology
Test
The most commonly used tests are antistreptolysin O (ASO) titer and antideoxyribonuclease B (ADB) titer.[2][20][33]
Perform the tests at two timepoints separated by 2 weeks for patient and close contacts.[33]
Order near the time of infection and then repeat to demonstrate a serologic rise.[33] A rise in serial antibody level, regardless of rapid test or culture result, supports recent immunologic response to group A streptococcus (GAS) infection.[33] Another sign of a recent infection is a falling titer around 6-8 weeks after the infection.[33]
Rising or falling titers (titers separated by 2 weeks).
Single ASO or ADB antibody level within 6 months after the initial onset of neuropsychiatric symptoms (positive if it is >95th percentile, using the laboratory's normal standard for children of comparable age), or ASO >1:480 or ADB >1:1280.[33]
Both ASO and ADB are elevated at >80% percentile for age in the same serum sample within 6 months after the initial onset of neuropsychiatric symptoms or initial set which is >80th percentile of normal age standard.[33]
However, note that documenting the presence of preceding GAS infection may be difficult, since GAS is common in elementary school children and infection may go undetected (some children have minimal or no symptoms of streptococcal pharyngitis). In some cases, the child may be diagnosed on the basis of a history of exposure to known GAS infection (particularly in a sibling or overnight stay with a friend/relative).
Result
elevated
CBC with differential
C-reactive protein (CRP)
erythrocyte sedimentation rate (ESR)
comprehensive metabolic panel
Test
As part of the basic blood workup.[20]
Result
normal or deranged
antinuclear antibodies (ANA)
immunoglobulins (IgG, IgA, IgM, IgE) with IgG subclasses
Test
As part of the basic blood workup.[20] Abnormal levels are present in patients with immunodeficiency, autoimmune disorders, or chronic infections.[2][20] Low immunoglobulins may be a sign of immunodeficiency. Very high IgG may be a sign of recent group A streptococcus (GAS) infection as described in acute rheumatic fever.[66]
Result
low levels may indicate immunodeficiency; high levels may indicate GAS or other infection
ferritin (iron) and transferrin saturation
Test
Hypoferritinemia and iron deficiency are more common in patients with PANS than in the sex- and age-matched general population.[4][71] Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with iron deficiency, consider the possibility of inflammation as the cause, especially if iron deficiency cannot be explained by diet and blood loss.[49]
Result
may be normal or low
Tests to consider
urinalysis
Test
In patients with urinary symptoms to assess for infection (presence of leukocytes and nitrites) and signs of dehydration (high specific gravity). In patients with gross hematuria or longstanding chronically ill patients, assess for inflammation which can manifest as proteinuria and/or hematuria.[2][20]
Result
normal
brain MRI
Test
Consider in patients with severe new-onset psychiatric symptoms, especially if one of the following is present:[20]
Cognitive/memory dysfunction (formal testing can pick up on more subtle problems)
New-onset severe headache
New-onset severe sleep disturbance
Behavior regression
Seizures.
Clinical brain MRIs are typically normal in PANS, although studies indicate statistically different basal ganglia changes when compared with controls.[37][38][39][40] T2 signal abnormalities, evidence of vasculitis, and demyelination should prompt consideration of other inflammatory brain disorders.
A brain MRI is not necessary if the clinical course has already been established to be relapsing-remitting.
Result
normal
electroencephalogram (EEG)
Test
Consider in patients with severe new-onset psychiatric symptoms, especially if one of the following co-occurs:[20]
Cognitive/memory dysfunction (formal testing can pick up on more subtle problems)
New-onset severe headache
New-onset severe sleep disturbance
Behavior regression
Seizures.
EEGs are typically normal in patients with PANS, although diffuse slowing has been observed. Prominent EEG changes including slowing and seizures should prompt full workup for autoimmune encephalitis. See Differentials. Spot EEGs may be adequate in most cases, but the transition from awake to sleep should be captured as signs of electrical status epilepticus in sleep may emerge during this transition.
An EEG is not necessary if the clinical course has already been established to be relapsing-remitting.
Result
normal
lumbar puncture
Test
Consider in patients with severe new-onset psychiatric symptoms, especially if one of the following co-occurs:[20]
Cognitive/memory dysfunction (formal testing can pick up on more subtle problems)
New-onset severe headache
New-onset severe sleep disturbance
Behavior regression
Seizures.
Cerebrospinal fluid is typically normal in children with PANS. If the patient has pleocytosis, IgG bands, high IgG index, or highly elevated protein or serum albumin quotient (Qalb), consider other inflammatory brain diseases.[67]
A lumbar puncture is not necessary if the clinical course has already been established to be relapsing-remitting.
Result
normal
polysomnogram
musculoskeletal imaging (MRI or ultrasound)
Test
Consider in patients who have achiness, pain, and stiffness in the morning or with prolonged stationary positions. Patients who have overwhelming psychiatric symptoms may not be able to appreciate and/or convey the subtle signs of arthritis.
The rate of arthritis, enthesitis, and inflammatory back pain is high in patients with PANS and their family members with PANS.[3][49] Most forms of arthritis in people with PANS are dry and therefore imaging is often needed to establish the diagnosis. Specialized joint ultrasound is preferred if a musculoskeletal ultrasound specialist is available. Where this is not available, MRI of involved joints may be used to confirm diagnosis if physical exam is limited (due to overlying pain processing disorder, overshadowing psychiatric symptoms, in the setting of dry arthritis).
Result
enthesitis, effusions in joints or peritendinous effusions, capsular thickening; synovitis may be present
swallowing studies
Test
Consider in patients with restricted food intake, particularly when related to fears of choking or vomiting.[20]
Result
may show dysphagia; discoordination of the muscles of the esophagus
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