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. Read more
In a longitudinal study of 1,037 people born in Dunedin, New Zealand in 1972 and 1973, most participants with attention deficit hyperactivity disorder (ADHD) in adulthood did not have the disorder as children. The study by Terrie E. Moffitt and colleagues in the American Journal of Psychiatry is the first prospective longitudinal study to describe the childhood of adults with ADHD.
When the study participants were children, about 6% were diagnosed with ADHD (mostly males). These children also had comorbid disorders, neurocognitive deficits, multiple genes associated with risk for ADHD, and some life impairment when they reached adulthood.
In adulthood, about 3% of the participants had ADHD (roughly equal between men and women), and 90% of these participants had no history of ADHD in childhood. The participants with ADHD in adulthood also had substance dependence and life impairment, and had sought treatment for the disorder. The researchers were surprised to find that these participants with adult ADHD did not show neuropsychological deficits in childhood, nor did they have the genetic risk factors associated with childhood ADHD.
If the findings of this study are replicated, researchers will have to rethink the current classification of ADHD as a neurodevelopment disorder that begins in childhood, and begin to determine how adult ADHD develops.
Editor’s Note: Before the publication of this article, most investigators (including this editor Robert M. Post) thought that virtually all ADHD in adulthood evolved from the childhood disorder, and if it did not begin in childhood, the diagnosis was suspect. I still believe the ADHD that appears in adulthood in patients with bipolar disorder is likely attributable to residual depression and anxiety or hypomania and that more concerted treatment of the patient to full remission will often result in much better attention, concentration, and ability to follow through and stay on task.
People with chronic fatigue syndrome, or myalgic encephalomyelitis, as it has also been called, suffer from extreme exhaustion and unrefreshing sleep. The condition has been considered mysterious, but new research is clarifying its symptoms and leading to more useful treatments. In 2015, a committee convened by the Institute of Medicine at the National Academy of Sciences decided to change the name of the condition to systemic exertion intolerance disease (SEID) to better reflect its symptoms and reduce stigma around the illness.
In recent years it had been determined that exercise regimens and cognitive behavioral therapy helped up to 60% of patients. Some new small studies show great results when patients are treated with anti-viral medications such as valacyclovir (Valtrex). Researcher Theodore Henderson reports that he has seen response rates as high as 85% in adults and 92% in adolescents.
Researchers now believe that some patients diagnosed with depression may actually have SEID. Symptoms like fatigue, exertion-induced malaise, brain fog, and impaired academic performance could be the result of the body’s reaction to a virus.
In a new study by ESM Eurelings and colleague in the journal International Psychogeriatrics, the inflammatory marker C-reactive protein differentiated between older people with symptoms of apathy versus symptoms of depression. Higher levels of C-reactive protein were found in those with symptoms of apathy. The researchers concluded that apathy may be a manifestation of mild inflammation in elderly people.
Both bipolar disorder and unipolar depression often begin in childhood or adolescence, but it can be difficult to distinguish the two using symptoms only. People with bipolar illness may go a decade without receiving a correct diagnosis. Researcher Jorge Almeida and colleagues recently performed a meta-analysis of previous studies to determine what neural activity is typical of children with bipolar disorder versus children with unipolar depression while processing images of facial emotion. They found that youth with bipolar disorder were more likely to show limbic hyperactivity and cortical hypoactivity during emotional face processing than youth with unipolar depression. Almeida and colleagues hope that this type of data may eventually be used to diagnose these disorders or to measure whether treatment has been successful.
In a recent retrospective study, people with bipolar disorder I, bipolar disorder II, and major depressive disorder were interviewed about a 14-year period of their illness, and several differences emerged.
People with bipolar disorder I described their illnesses as including more psychomotor retardation (slowing of movements) and more psychotic features. People with bipolar disorder II had more mixed states than both people with major depression and people with bipolar I disorder. They also had less psychomotor slowing than people with bipolar I disorder.
Another purpose of this study by Andrew Frankland and colleagues in the Journal of Clinical Psychiatry, was to determine the effectiveness of the Probabalistic Approach to Bipolar Disorder, a statistical method for differentiating diagnoses. The approach was successful in differentiating both bipolar subtypes from major depression, but not in differentiating between the bipolar subtypes.
Researcher Kiki Chang discussed pediatric acute onset neuropsychiatric syndrome (PANS), an inflammatory illness with psychiatric symptoms, at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry. PANS is diagnosed when following an infection, a child who had previously been well has a sudden onset of obsessive-compulsive disorder (OCD), mood dysregulation, tics, food restriction behaviors, and a variety of other symptoms. A similar syndrome called PANDAS (for pediatric acute onset neuropsychiatic disease associated with streptococcal infections) was first identified in children recovering from strep throat. The children suddenly developed OCD behaviors and tics after a streptococcal infection.
However, PANS is associated with a variety of infections, including viruses and other infections that do not involve streptococcus bacteria. PANS syndrome is typified by acute onset of obsessive compulsive disorder and food restrictions as well as two or more of the following symptoms: anxiety, mood swings and depression, irritability and aggression, behavioral regression, decreases in school performance, sensory motor abnormalities, and somatic alterations such as decreased sleep and urinary incontinence, frequency, and/or urgency. Tics are not part of the formal diagnosis, but are present in about 50% of patients.
In Chang’s experience, the syndrome emerged 65% of the time in relationship to streptococcal infections, 13% with mycoplasma infections, 58% with viral infections, 39% in association with sinusitis, and 16% with otitis (inflammation of the ear). Increases in blood flow in the basal ganglia and increases in its volume likely occur due to antibodies that the immune system produces to fight infection, but which instead attack elements in the brain’s striatum, including tubulin, calcium calmodulin kinase II, lyso-GM-1, and dopamine D1 and D2 receptors.
Chang suggested that a diagnostic workup for PANS should include: a complete blood count and screening for red blood cell sedimentation rate, mycoplasma antibodies IgG and IgM, anti-nuclear antibodies (ANA), ferritin (a protein that stores iron in blood), celiac disease, and other laboratory measures that are commercially available in a panel produced by the company Moleculera Labs. A more detailed description of the PANS syndrome and its diagnosis and workup is available in the most recent 2014 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.
In a related poster, Jennifer Frankovich, another researcher in Chang’s lab, reported that 62% of family members of children with PANS had a history of autoimmune disorders.
New research suggests that the ratio of cortisol to C-reactive protein (CRP), a marker of inflammation, may be a biomarker of depression that affects men and women differently. In women, lower ratios of cortisol to CRP were associated with more severe depression symptoms, including poor quality sleep, sleep disturbances, and decreased extraversion. In men, higher ratios of cortisol to CRP were associated with more daytime disturbance and greater anxiety. The study by E.C. Suarez et al. was published in the journal Brain, Behavior, and Immunity.
Further work must be done to confirm whether low cortisol and high inflammation predicts depression in women, while the opposite (high cortisol and low inflammation) predicts depression in men.
Three articles in the September 2014 issue of the journal Psychiatric Annals (Volume 44 Issue 9) discussed differentiating pediatric bipolar disorder from attention deficit hyperactivity disorder (ADHD). The first article, by Regina Sala et al., said that reasons to suspect bipolar disorder in a child with ADHD include:
- The ADHD symptoms appear for the first time after age 12.
- The ADHD symptoms appear abruptly in an otherwise healthy child.
- The ADHD symptoms initially responded to stimulnts and then did not.
- The ADHD symptoms come and go and occur with mood changes.
- A child with ADHD begins to have periods of exaggerated elation, grandiosity, depression, decreased need for sleep, or inappropriate sexual behaviors.
- A child with ADHD has recurring severe mood swings, temper outbursts, or rages.
- A child with ADHD has hallucinations or delusions.
- A child with ADHD has a strong family history of bipolar disorder in his or her family, particularly if the child does not respond to appropriate ADHD treatments.
The second article, by this editor Robert Post, Robert Findling, and David Luckenbaugh, emphasized the greater severity and number of symptoms in childhood onset bipolar disorder versus ADHD. Children who would later develop bipolar disorder had brief and extended periods of mood elevation and decreased sleep in the early years of their lives. These, along with pressured speech, racing thoughts, bizarre behavior, and grandiose or delusional symptoms emerged differentially from age three onward. In contrast, the typical symptoms of ADHD such as hyperactivity, impulsivity, and decreased attention were equal in both diagnoses.
In the third article, Mai Uchida et al. emphasized the utility of a family history of bipolar disorder as a risk factor. Moreover, a child with depression plus ADHD is at increased risk for a switch into mania on antidepressants if there is a family history of mood disorders, emotional and behavioral dysregulation, subthreshold mania symptoms, or psychosis.
The differential diagnosis of ADHD versus bipolar disorder (with or without comorbid ADHD) is critical, as drug treatment of these disorders is completely different.
Bipolar disorder is treated with atypical antipyschotics; anticonvulsant mood stabilizers, such as valproate, carbamazepine, or lamotrigine; and lithium. Only once mood is stabilized should small doses of stimulants be added to treat residual ADHD symptoms.
ADHD, conversely, is treated with short- or long-acting stimulants such as amphetamine or methylphenidate from the onset, and these may be augmented by the noradrenergic alpha-2 agonists guanfacine or clonidine. The selective noradrenergic re-uptake inhibitor atomoxetine is also approved by the Federal Drug Administration (FDA) for the treatment of ADHD. The dopamine-active drug bupropion and the anti-narcolepsy drugs modafinil and armodafinil have mild anti-ADHD effects but have not been FDA-approved for that purpose.
At the 2014 meeting of the International Society for Bipolar Disorders, researcher B.N. Kim discussed symptoms that could distinguish between bipolar disorder and attention deficit hyperactivity disorder (ADHD) in childhood. Both disorders are characterized by decreased attention, concentration, and frustration tolerance, and increased activity, impulsiveness, and irritability.
Kim shared several differential symptoms that are more indicative of a bipolar diagnosis and that are inconsistent with a simple ADHD diagnosis (and this editor Robert Post has added several more). Signs and symptoms that suggest bipolar disorder and not ADHD include: decreased need for sleep, brief and extended periods of euphoria, hypersexuality, delusions, hallucinations, suicidal or homicidal impulses and/or actions, extreme aggression, and multiple areas of extreme behavioral dyscontrol. ADHD, on the other hand, is characterized by more difficulty focusing attention, and by less extreme symptoms in general.