A PANS Case Study, Immune Treatment Reduced Psychiatric Symptoms
Pediatric acute neuropsychiatric syndrome (PANS) is a little-known syndrome in which a child has an acute onset of psychiatric symptoms following a bacterial or viral infection, when the antibodies generated to fight the infection instead attack neurons in the brain. The behavioral alterations can be severe and resistant to the usual psychotropic drug treatments. PANS often requires antibiotics and immune-targeted therapies.
The following is a case report of a real child who had a sudden onset of depression and violence after getting sick with the flu, pneumonia, and a strep infection at the age of 4. (Names have been changed for privacy.)
Anne contacted this editor (Robert M. Post) seeking a consultation on her 6-year-old son, Jake. Two years earlier, he had suddenly become difficult—depressed, angry, and even violent. This coincided with the emergence of obsessive compulsive symptoms and urinary incontinence. He went from being able to read short sentences in pre-kindergarten, to being cognitively dull and not even able to recognize letters of the alphabet. He had been diagnosed with a mood disorder, and Anne was told it was probably bipolar disorder. But he didn’t respond to any of the typical medications, and suffered side effects including hallucinations, nightmares, bowel accidents, and worsening depression.
The best results came with the atypical antipsychotic risperidone. While it didn’t reduce all of Jake’s symptoms, Anne described it as “heaven” compared to earlier treatments. But Jake’s levels of prolactin started to increase, and he lost bladder control, so he had to stop taking risperidone. Jake’s doctor tried 18 different medication regimens with 8 different medications in less than a year without finding one that worked well. Jake had a horrible time in school, and Anne fretted about the lack of an effective, stable medication, saying, “He’s actually worse than I’ve ever seen him.”
Dr. Post recommended that they consider using high doses of quetiapine and valproate for Jake’s aggression and behavioral dyscontrol, along with the antioxidant N-acetylcysteine and vitamin D3. However, given that Jake’s symptoms were severe, involved cognitive and neurological abnormalities, and had begun after a flu-like illness, and was unresponsive to conventional treatment, Dr. Post suggested that Anne get Jake checked out for PANS and start charting Jake’s mood on a daily basis.
Jake began taking higher doses of quetiapine and valproate, and improved to the point that Anne said they restrained him only once a day, rather than four times per day. But his behavioral dyscontrol continued. In one memorable incident, after feeling picked on by other children at a baseball game, he lashed out at Anne, kicking her in the face with his cleats and punching her glasses off her face.
Anne told Dr. Post that the family had visited a neurologist, who said that she had never heard of PANS and suggested that Anne would have to travel across several states to see Dr. Post if she wanted to pursue that diagnosis.
Dr. Post encouraged Anne to keep looking for a doctor who would take the PANS idea seriously. He sent her a comprehensive review article about PANS by Dr. Kiki Chang and colleagues published in the Journal of Child and Adolescent Psychopharmacology in 2014.
This past June, Anne found a doctor who understood PANS and was willing to run the appropriate tests on Jake. The tests revealed that Jake had at one time been infected with the bacteria mycoplasma. His immune system mobilized to fight the infection, but the antibodies it produced (IgG and IgM) also attacked his brain. The doctor recommended anti-inflammatory and antibiotic treatments to target the immune response.
In September, Anne wrote that Jake has made a dramatic improvement. In the beginning of June, Jake was “all over the place,” ranging from severe mania to high depression. From filling out daily mood charts (available on our website https://bipolarnews.org under Mood Charting), Anne could see that within days of beginning treatment for PANS, Jake’s mood stabilized. While he still has some symptoms, Anne says that he has not had more than a mild mood swing since June.
Jake’s current medications include 200 mg a day of the anti-inflammatory ibuprofen and 250mg a day of the antibiotic azithromycin, plus 20 billion CFUs of a probiotic, 1000 UI of vitamin D3, 50mg of 5HTP, 10mg of Claritin, 300mg twice a day of oxcarbazepine (Trileptal), 0.1mg twice a day of Clonidine ER, 15mg of Zinc, and 15mg twice a day of Armour Thyroid.
Anne says, “My understanding is this is a long and curvy road, but I could not be happier to at least be on the right street.” The next step for Jake would be IVIG, or intravenous immunoglobulin, a blood product that contains antibodies from over a thousand blood donors. Eventually they hope that Jake can be weaned off the Trileptal and Clonidine.
The following are some highlights from Chang’s article on the diagnosis, workup, and treatment of PANS.
Diagnosing PANS
The diagnostic criteria for PANS are as follows:
A. Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake
B. Concurrent presence of additional neuropsychiatric symptoms (with similarly severe and acute onset), from at least two of the following seven categories:
- Anxiety
- Emotional instability and/or depression
- Irritability, aggression, and/or severely oppositional behaviors
- Behavioral (developmental) regression
- Deterioration in school performance (related to attention deficit hyperactivity disorder (ADHD) -like symptoms, memory deficits, cognitive changes)
- Sensory or motor abnormalities
- Somatic signs and symptoms, including sleep disturbances, bedwetting, or urinary frequency
C. Symptoms that are not better explained by a known neurological or medical disorder
In the article, Chang writes, “Many children with PANS are extremely ill, with extreme compulsions (licking shoes, barking), motor and phonic tics (whooping, wringing hands), behavioral regression, and terrifying episodes of extreme anxiety or aggression….”
“By definition, the individual PANS symptoms overlap with a variety of psychiatric disorders, such as OCD, Tourette’s syndrome, ADHD, depression, and bipolar disorder. However, the acuity of onset and simultaneous presentation of these symptoms differentiate PANS from these psychiatric conditions. The PANS diagnosis is, therefore, limited to cases with acute-onset symptoms in multiple domains.”
Testing for PANS
Chang recommends that all patients meeting the criteria for PANS should have the following labwork done:
- Complete blood cell count with manual differential
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
- Comprehensive metabolic panel
- Urinalysis (to assess hydration) and to rule out inflammation for children with urinary complaints; clean-catch urine culture for those with pyuria
- Throat culture, anti-streptolysin O (ASO) and anti-DNAse B
The following laboratory tests should also be considered:
If there are elevated inflammatory markers, fatigue, rashes, or joint pain, antinuclear antibody (ANA) or fluorescent antinuclear antibody (FANA) should be obtained; if ANA is elevated, proceed with lupus workup.
Antiphospholipid antibody work up should only be pursued if the patient has chorea, petechiae, migraines, stroke, thrombosis, thrombocytopenia, or levido rash. Workup includes: anticardiolipin antibody, dilute Russell’s viper venom time (dRVVT), b 2-glycoprotein I antibodies. If abnormal liver function tests or Kayser–Fleisher rings are present, there is a need to evaluate for Wilson’s disease with ceruloplasmin and 24 urine copper tests.
Infectious disease evaluation: “The most commonly observed antecedent infection seems to be upper respiratory infection, including rhinosinusitis, pharyngitis, or bronchitis.” Mycoplasma pneumonia, influenza, Epstein Barr virus, and Borrelia burgdorferi (Lyme disease) are often involved.
Immunodeficiency screening should proceed in multiple steps, complemented with repeated clinical evaluation of the patient. Initial workup should include the following:
- Lymphocyte subsets (T, B, natural killer [NK] cells) with CBC with manual differential
- Quantitative immunoglobulins (IgG, IgA, IgM, IgE) with IgG subclasses
- Vaccine responses (Pneumococcus and tetanus antibody titers)
Treating PANS
Treatment can include: antibiotics, anti-inflammatories, steroids, immune-suppressants, IVIG (a mixture of antibodies), or plasmaphoresis.
In a presentation that Dr. Post heard Dr. Chang give, Chang indicated that many children with PANS are severely ill for long periods of time (as Jake was) before the correct diagnosis is made and appropriate treatment begun.
Chang concludes his article by saying that “[r]eferral to a neurologist or rheumatologist can be helpful in some cases, but should be focused on specific signs or symptoms of concern, as the subspecialists may not be experienced with the evaluation of psychiatric symptomatology. Therefore, the responsibility of evaluating PANS falls to primary care clinicians and child psychiatrists.”
Dr. Post adds that this case study shows the value of collecting daily mood ratings that can graphically depict symptom variation, progression, or improvement. We offer several types of daily rating forms for free download on our website (bipolarnews.org, click the tab for Mood Charting and look for the Monthly Mood Chart Personal Calendar). Another option for parents who want to chart their child’s mood and behavioral problems is to join our online Child Network, where they can enter weekly ratings of their child’s anxiety, depression, attention deficit, oppositional, or manic symptoms on a secure website. This takes just a few minutes per week and produces a helpful graph that can be printed and sent to the child’s doctor. To learn more about joining the Child Network, visit our website at bipolarnews.org and click on the tab for the Child Network.
