Image

Diagnosis

Image

Diagnosis

PANDAS and PANS is a clinical diagnosis based on the collection of signs, symptoms, medical history, and laboratory findings that cannot be explained by any other neurological or medical disorders. Currently, there is not a 100% definitive test for PANDAS or PANS.

If you suspect your child has PANDAS or PANS, the following labs, in addition to completing the symptoms scales can help aid your medical provider in making a proper diagnosis.
BASIC BLOOD WORK:
  • IgE Level
  • IgA, IgM,
  • IgG (subclass 1, 2, 3, 4)
  • CBC
  • ANA
  • Ferritin
  • B-12
  • Vitamin D
VIRAL/BACTERIAL TESTING:
  • Strep throat culture, 48 hour culture or perianal culture
  • Bacteria & Virus Blood Work:
  • Antistreptolysin O  (ASO)
  • Anti dNase B
  • Streptozyme
  • Lyme Disease and co-infections
  • Mycoplasma Pneumoniae IgA & IgM
  • Pneumococcal Antibody Titers
  • Epstein Barr Virus Panel
  • Coxsackie A & B Titers
  • HHV-6 Titers
ADDITIONAL TESTING:

Cunningham Panel* – autoimmune autoantibody levels: Dopamine D1 receptor, Dopamine D2L receptor, Lysoganglioside GM1, Tubulin, & CaM Kinase II.

BASIC BLOOD WORK:
  • IgE Level
  • IgA, IgM,
  • IgG (subclass 1, 2, 3, 4)
  • CBC
  • ANA
  • Ferritin
  • B-12
  • Vitamin D
VIRAL/BACTERIAL TESTING:
  • Strep throat culture, 48 hour culture or perianal culture
  • Bacteria & Virus Blood Work:
  • Antistreptolysin O  (ASO)
  • Anti dNase B
  • Streptozyme
  • Lyme Disease and co-infections
  • Mycoplasma Pneumoniae IgA & IgM
  • Pneumococcal Antibody Titers
  • Epstein Barr Virus Panel
  • Coxsackie A & B Titers
  • HHV-6 Titers
ADDITIONAL TESTING:

Cunningham Panel* – autoimmune autoantibody levels: Dopamine D1 receptor, Dopamine D2L receptor, Lysoganglioside GM1, Tubulin, & CaM Kinase II

Strep

 

The Complexity of Strep

INTRACELLULAR

The bacteria can adhere to the epithileal cells of the throat or nasal passages. Important to PANDAS cases: because at ONSET often the strep is reported as persistent and resistant to eradication. One child required nasal surgery. Strep was found in the biopsy.

A peer-reviewed article on Intracellular Strep:
(2008) Thulin, et al, How Group A Streptococci Hide in Macrophages

SOME SEROTYPES CAN BECOME MUCOID

The big culprit for Rheumatic Fevers is M18. If it develops a “mucoid shield” – typical antibiotics like penicillin or Augmentin cannot pierce the cell wall. Doctors must experiment with stronger antibiotics to rid the body of these.

The study below is highly complex – but it is shown here to illustrate the complexity of this bacteria:(2000) Cunningham, Pathogensis of Group A Streptococcal Infections.

MOLECULAR MIMICRY

This is a natural process by where the human body is attempting to rid itself of the strep bacteria. It is the causative factor for Rheumatic Fever and other virulent strep illnesses, and, probably – initially with PANDAS. Below are two studies attempting to explain this phenomena in PANDAS.

Below are two studies attempting to explain this phenomena in PANDAS.
Swedo and Grant (2004), Annotation: PANDAS: a model of human autoimmune disease.
Snider and Swedo (2003), Post-streptococcal autoimmune disorders of the central nervous system.

Non-Strep Triggers

Strep throat is very common in children. Typically, the symptoms are fever, sore throat, and white spots on tonsils. Some children present with an upset stomach, headache, and more. Additionally for some people, they may not exhibit any symptoms. For PANDAS children, the behavior changes are their indicating symptoms of a possible infection.

According to Dr. Susan Swedo, PANDAS children should not be classified as “strep carriers” since their PANDAS symptoms are an immune reaction. A person who is a classic strep carrier creates absolutely no negative reaction at all to the bacteria.

STREP IN OTHER PLACES OF THE BODY

In addition to the throat, strep can occur in the sinuses, in the ears, in the gut, on the skin, in the vagina, and peri-anal strep.  A throat swab will not give you positive result for strep that is occurring somewhere else in the body.

STREP SWAB RAPID TEST AND CULTURE

A throat swab is the easiest and least invasive way to test for strep throat.  If the child tests positive, treatment can begin quickly and the correlation between strep and the onset of symptoms can begin to be investigated.

If an in-office strep swab renders a negative test result make sure your office also CULTURES a swab since there is a chance for a false negative rapid test.  There are some offices that will only do this upon request.

If your child or a family member tests positive for strep, schedule a follow up strep test two weeks after finishing all antibiotics.

TESTING FAMILY MEMBERS

It is important to swab all family members to be sure no one is asymptomatic when infected or a possible strep carrier. Carriers will often not show any strep symptoms, but if tested, will be positive for strep. A carrier will need one or two doses of antibiotics to rid themselves of strep.

Testing family members will lower your child’s chances of being re-infected. Also, some PANDAS children even react to exposure to strep.

STREP TESTING VIA BLOOD WORK

Strep ASO
Anti-DNase B Titer
Streptozyme

NORMAL TITERS DOES NOT ALWAYS MEAN STREP IS NOT PRESENT

In all literature regarding Rheumatic Fever, it is commonly known that strep has the ability to create “molecular mimicry” of the child’s own autoimmune response, therefore stopping the titer-rising process.

Also, according to the Shet et. al (2003) study:

  • Only 54% of children with strep showed a significant increase in ASO.
  • Only 45% showed an increase in anti–DNase B.
  • Only 63% showed an increase in either ASO and/or anti–DNase B.

In short, this means, not all children who have strep will have a rise in titers.

THE MAJORITY OF STREP INFECTIONS ARE MISSED

According to the Hysmith et. al (2017) study:

  • 65% of new strep of new group A strep infections caused no symptoms yet were immunologically significant

 

Even though Strep is the most cited trigger for PANDAS and PANS, other bacteria, viruses, and environmental factors can create the misdirected immune response.

EXAMPLES OF NON-STREP INFECTIOUS TRIGGERS

MYCOPLASMA PNEUMONIAE
Mycoplasma Pneumoniae is also known as Walking Pneumonia

STAPH INFECTIONS
Staph can occur in multiple places in the body; on the skin, in the nose, and it has even been found in the biopsy results on tonsils post tonsillectomy

LYME DISEASE
The Traditional Western Blot should be done when Lyme is suspected. The Igenex Lyme test shows antibodies that MAY be present. Approach Igenex testing with a doctor who looks at this from a comprehensive understanding of the immune system and PANDAS/PANS.

INFLUENZA

COXSACKIE VIRUS

EPSTEIN BARR VIRUS

HERPES SIMPLEX VIRUS

OTHER POSSIBLE TRIGGERS

Once the autoimmune process is in place, other things may worsen or trigger symptoms in PANDAS/PANS children. Not every child will react to non-strep triggers. If your child is experiencing a flare of symptoms and no infection is present, the following are some possible suspects:

EXPOSURE TO ILLNESS
In PANDAS and PANS children, sometimes exposure to an illness can trigger symptoms.

ALLERGIES
This includes seasonal allergies.

STRESS

CHLORINE

DIET
Some families find changing the child’s diet helps. This may include ‘clean eating’, and eliminating certain foods such as gluten, dairy, etc.

YEAST OVERGROWTH
Antibiotics run the chance of also killing off the “good bacteria” in their body. This could result in an overgrowth of yeast or candida, which can occur in multiple places in the body, including the gut. If you suspect yeast overgrowth, discuss this your provider.

Immunological Workup

Some children with PANDAS or PANS may have underlying immunodeficiencies.  The following tests are used in making that diagnosis. A clinical diagnosis of  IgG deficiency may allow for insurance coverage for IVIG.

RECOMMENDED TESTS
  • CD4 This test measures generally over-reactive immune response.
  • IgG Subclass 1, 2, 3, 4 for total immunoglobulin levels
  • IgA and IgM

For an explanation of possible deficiencies, please reference IgG Subclass Deficiency and Specific Antibody Deficiency .

MRI/EEG/PET

MRI

A Pediatric Neurologist request an MRI. See the following for information on MRI as it relates to these disorders:

  1.    SWEDO/SNIDER 2003, Post-Streptococcal Autoimmune Disorders of the CNS.
  2.    SWEDO, et al 2000, MRI Assessment of Children with OCD & Tics Associated with Strep.
  3.    MABROUK/EAPEN 2008, Challenges in the Identification and Treatment of PANDAS: A Case Series.
EEG

A few children have been found to have irregular EEG’s. This could be PANDAS or some other frontal lobe seizure issue which can create separate psychological or physical issues.

An EEG is also something to look into if a child experiences sleep abnormalities. A sleep study that results in abnormal findings may expedite receiving treatment.

PET SCAN
The Possible Future Test for PANDAS

In “Basal ganglia inflammation in children with neuropsychiatric symptoms” by Drs. Kumar, Williams, Musik and Chugani shows a significant difference in brain inflammation patterns between PANDAS children and those with Tourette Syndrome (TS). This information was obtained through special PET scanning.

These findings are very important because it reinforces the stance that PANDAS is not just Tourettes or OCD, but it is different and requires different treatment protocols. It also signifies the difference in the etiology, or cause, of the two disorders.

Basal Ganglia Imaging Study by Dr. Harry Chugani

The rogue white blood cells that cause PANDAS affect the basal ganglia of the brain. The basal ganglia are several brain structures located in the center of the brain. They function as a communication route to other parts of the brain and are partly responsible for the movement of our body. Other parts of the basal ganglia are involved in memorization, cognitive and emotional processing, and again initiating movement. There is still much to be learned about how this part of our brain functions. It is theorized that PANDAS causes an inflammation of the basal ganglia. A 1999 study by Ranjit C. Chacko, M.D. showed a connection between OCD and the basal ganglia.

Now, Dr. Harry Chugani at Children’s Hospital of Michigan, is studying the potential use of PET scans as diagnostic tools for PANDAS Dr Chugani states that the basal ganglia are not hard to detect on an MRI scan. In fact, the basal ganglia are large structures. However, the MRI scan is not useful for detection of abnormal microscopic, neurological functioning in the basal ganglia because MRI scans look at anatomy, i.e., tissue density and damage, water displacement, inflammation of tissue (and not the neurological function of this part of the brain). PET scans, or Positron Emission Tomography scans, may be used instead of, or in addition to, magnetic resonance imaging (MRI) scans. This gives anatomic and functional information.

The PET scan works by using PK-11195, a radioactive material, to target the inflammatory cells of the brain.  This chemical is attracted to inflammatory cells and gives information on how the basal ganglia are functioning. Some of the PET scans on PANDAS children are identifying inflammation in the basal ganglia. This may be useful as the long awaited confirmation of PANDAS that parents have sought.

Dr Chugani said, “By finding PET scan evidence of abnormality in the basal ganglia, we may now have a biomarker for PANDAS Indeed, following IVIG in some PANDAS subjects, the abnormality in basal ganglia has gone away on repeated PET scan. These studies are rather preliminary, on a limited number of subjects, and much more work needs to be done.”

Cunningham Panel

THE TEST

The Cunningham Panel™  of Tests determines the “likelihood of the patient’s condition being autoimmune in nature”, including possible PANDAS and PANS. The test measure 5 assays and is commercially available by Moleculera Labs.

Dr. Cunningham’s research, which led to this test, measured cross-reactive antibodies that are elevated in a PANDAS child’s brains. Many children got assistance with PANDAS treatment from Immunologists if the results of this blood test indicate PANDAS-like antibody levels.

PHYSICIANS:

To order The Cunningham Panel™  of Tests within the United States, visit www.moleculeralabs.com.

INTERNATIONAL TESTING

Patients and Physicians outside the United States can find more details here, https://www.moleculeralabs.com/international-ordering-cunningham-panel/.

THE RESEARCH BEHIND THE TEST

In the following studies by Dr. Cunningham, et al., it is shown that movement disorders in Sydenham Chorea patients – a movement problem caused only by strep – and PANDAS children are similarly elevated. In both illnesses the basal ganglia are activated by a negative autoimmune reaction to strep.

This is important to show doctors so they understand that your child is not simply suffering from a psychological issue and may be having movement or mood issues due to strep antibody cross-reactivity from auto-antibodies called anti-lysoganglioside and anti-tubulin.

Symptom Scales

PANDAS/PANS SYMPTOM SCALE

PANDAS and PANS are clinical diagnoses that are heavily reliant on symptom presentation.

A clinical diagnosis is a diagnosis not solely based on a diagnostic test such as a blood test. Rather, the diagnosis is based on the collection of signs, symptoms, medical history, and laboratory findings. Currently, there is not a 100% definitive test for PANDAS or PANS.

Showing the severity of symptoms, the duration, and the onset are important tools in determining a possible diagnosis.  The scale below will help parents present their child’s symptomatology.

The following scale is based on the clinical experience of Susan Swedo, M.D., Miroslav Kovacevic, M.D., Beth Latimer, M.D., and James Leckman, M.D., with the help of Diana Pohlman, Keith Moore and many other parents.

PEDIATRIC ACUTE NEUROPSYCHIATRIC SYMPTOM SCALE

OCD/TIC SCALES

The following scales are what doctors use to measure the severity of OCD and TICs. Review these scales and show them to your doctor and communicate that your child went from normal levels (1-5) to abnormal (10 and above) overnight. OCD may present as severe anxiety. Do not assume your child does not fall into the realm of OCD because they do not show the “stereotypical symptoms” of OCD, such as hand obsessive washing and fear of germs.

OCD Scale and Tic Scale