PANS and PANDAS

Inspired by a colleague

PANS AND PANDAS: AN INTERVIEW WITH DR. MIROSLAV KOVACEVIC

9/4/2018 

Dr. Kovacevic is a board certified pediatrician and one of the first pediatricians in the country to begin treating children with PANDAS.

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How did you first learn of PANS/PANDAS and what motivated you to begin treating children with PANS and PANDAS?

It was an accident. In 1999 a child of a friend, who was a pediatrician, had a condition nobody could explain so that is how it started. I found a small five liner in the literature referring to PANDAS and tried to contact the NIH. I did get in touch with them and was told they were doing some research on it. After that, I had kids were so incapacitated and had been through five or six institutions. I tried treatment for PANDAS, it worked, and from them on I continued to treat children who had PANDAS.

Do you ever treat children who did not have an abrupt or acute onset, and if so, do they respond similarly to children who did have an abrupt onset?

There has been an evolution of understanding of PANS and PANDAS. The first ten to twelve years, the sudden onset was a must. When a child starts having symptoms at two to three years of age, it is more difficult to recognize the onset. Certainly there are children who fulfill all the criteria aside from abrupt onset for whom treatment is successful.

Have you had any patients who had been diagnosed with autism who ended

up actually having PANS?

Yes, but let’s be specific on that. I have had a number of children who were initially diagnosed with PDD-NOS that later on turned out to be PANDAS.

And did their symptoms of autism remit with treatment for PANDAS?

Yes, their symptoms of autism went away with treatment.

What about children who had been diagnosed with bipolar disorder, oppositional defiant disorder, etc?

Any time you have children with a long history of neuropsychiatric symptoms, you will have a whole slew of diagnoses--anxiety, oppositional defiant disorder, bipolar disorder, etc. That really has been the story. You have all these diagnoses established at different times. The symptoms evolution of PANDAS over time differs from child to child. A child can have one episode where OCD is the main feature. The next episode could be tics or irrational fears. Children's symptoms do change from episode to episode and advance with age.

What are the ages of the youngest and the oldest PANS patients you’ve ever diagnosed?

The youngest patient with confirmed PANDAS was 3.5 years old and presented with acute anorexia. The oldest was 48. Up until 2010, PANDAS was considered to be exclusively pediatric. I started to question this and found that these children do not outgrow PANDAS. It doesn’t go away so they retain the symptoms. It appears that unless children with PANDAS are treated, it is a lifelong condition.

In your opinion, why hasn’t PANS/PANDAS moved beyond controversy?

I think recently, as recently as the past two to three years, it has moved beyond controversy. I think one of the reasons it has been difficult is we still have the division in medicine into mental and physical symptoms. There is mental illness which in my opinion doesn’t exist. There is physical illness with mental illness symptoms. Children with PANDAS often have no physical symptoms of illness so they’re immediately pronounced behavioral. There is the  implication that the child could do something about their behavior if they tried hard enough. That is unfair.

The second problem is there is a division between mental and physical illness that is deeply rooted into society. There are two groups of patients and they are treated differently. In mental illness, there is usually not normal testing, lab testing, etc. that is required in physical illness. Again, switching camps is very hard.

What percentage of your patient population requires IVIG?

Again it is a matter of age. In my opinion, and I have followed patients as long as 19 years, it appears all patients with a diagnosis of PANDAS eventually do need IVIG as the ultimate

resolution. Yes, you can put these patients into remission with antibiotics and steroids, however, based on my experience, the occurrence is almost inevitable later in life. Let me give you an example. A number of years ago, I had a child with acute onset at eight years old, returning from Europe. We treated with antibiotics and he did well. It happened that I followed the child as pediatrician at that time. I was witness to his perfectly normal health for five to six years. At age 14, he woke up with full blown picture of PANDAS. I believe all children with PANDAS will need IVIG sooner or later.

How often is more than one course of ivig necessary?

Again historically, it all depends on what is done prior to IVIG. Until 2010 we basically would treat with IVIG if the child's clinical picture required it. I saw a 18-20% recurrence. In 2010 we started look at recurrence more closely and tonsils and adenoids were suspected as a trigger.  We started to employ tonsillectomy and adenoidectomy before treating with IVIG. Preliminary evidence is 5% or less are now needing repeat IVIG. Somewhere between

one in ten and one in twenty children.

Do you see a difference in outcomes when children are treated promptly

versus when they have been sick for years?

Actually that is not necessarily the case. It appears the effectiveness is solely dependent upon the age, not the duration, intensity, or quality of symptoms. From my population, in boys between the ages of six and 13, and girls between the ages of six and 12 who are treated with IVIG, the response rate appears to be 75-77%. After twelve in boys and thirteen in girls,the effectiveness starts slowly waning down. The effectiveness dissipates entirely by late twenties or early thirties. The importance of early diagnosis is not necessarily related

to better outcomes.  Clearly improving quality of life for children and parents because they know what they are dealing with is an importance that should be attached to early diagnosis.

Is there any new research you're excited about that you think will improve quality of life for children with PANS and PANDAS?

There are a number of things we are looking at this moment. Honestly I am excited about any improvements we can get. One thing that is being looked at is if a specific strain of group A strep is causing PANDAS. Group A strep is not a unified group of germs. There are 120 different strains so the question before us is, is there a particular strain that is likely to cause PANDAS? The second thing is the possible genetic contribution to the development of PANDAS. We do have anecdotal evidence that susceptibility to PANDAS is likely inherited but

we don’t have specific data. Finding this out could help a great deal.

Thank you to Dr. Kovacevic for taking the time to be interviewed by FCND Founder and President, Anna Conkey.

http://www.neuroimmune.org/kovacevic/pans-and-pandas-an-interview-with-dr-miroslav-kovacevic

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Swedo SE, Seidlitz J, Kovacevic M, Latimer ME, Hommer R, Lougee L, Grant P. Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):26-30.

Abstract

BACKGROUND:

The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described >15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS.

METHODS:

A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). RESULTS were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48).

RESULTS:

As described in the original PANDAS cohort, males outnumbered females (95:45) by ∼ 2:1, and symptoms began in early childhood (7.3±2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86-92%), school issues (75-81%), sleep disruptions (71%), tics (60-65%), urinary symptoms (42-81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections.

CONCLUSIONS:

The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may preclude a diagnosis of PANDAS in some children with acute-onset OCD, they do appear to meet criteria for pediatric acute-onset neuropsychiatric syndrome (PANS).

Kovacevic M, Grant P, Swedo SE. Use of intravenous immunoglobulin in the treatment of twelve youths with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):65-9.

Abstract

This is a case series describing 12 youths treated with intravenous immunoglobulin (IVIG) for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Although it is a clinically based series, the case reports provide new information about the short-term benefits of IVIG therapy, and are the first descriptions of long-term outcome for PANDAS patients.