A nine-year-old girl was evaluated for involuntary lower facial movements that became progressively worse over the preceding 6 weeks. Initially, the movements were brief, involuntary shoulder shrugs that occurred several times each day. They gradually became more exaggerated and occurred more frequently. After several weeks, her mother began to notice hiccup-like movements that occurred without any sound, in conjunction with occasional facial grimacing. The movements were exacerbated by activity and occurred more frequently in the evenings. In addition, her parents noted that she had increased emotional lability since the onset of these movements. She was referred to the infectious disease service after her primary care physician discovered that she had an anti-streptolysin O (ASO) titer of 1:340.
Her past medical history and family history were unremarkable.
On physical examination, she was a healthy-appearing girl. Throughout the examination, she made frequent facial grimaces. Her growth parameters were all in the 50th percentile. Her vital signs were unremarkable. Her general physical examination was normal. The neurologic examination was entirely normal save for the grimaces and repeated soundless abdominal wall movements resembling hiccups.
Robert Listernick, MD, moderator: How should we approach a child with a movement disorder?
Joshua Goldstein, MD, pediatric neurologist: Movement disorders can be divided into two groups - hyperkinetic and hypokinetic movements. Hypokinetic disorders include Parkinson's disease and the various muscle dystonias. Hyperkinetic movement disorders include such entities as tics, chorea, tremors, and myoclonus. Distinction among the various types of movements may be difficult; often the best way to accurately classify a movement disorder is to videotape the patient and have several specialists view the tape.
Dr. Listernick: Can you help us differentiate between these various movements clinically?
Dr. Goldstein: Dystonie patients have one or more muscle groups that remain in a fixed, abnormal position, usually for just several seconds. Tremors are rhythmic movements. Myoclonus is a rapid brief jerk. Tics may be very difficult to distinguish from chorea. In fact, in the mid-nineteenth century, tics were first described as a false chorea. Tics are very stereotypical, the same movement repeated constantly. Chorea is more random and interferes with planned actions. Tics may cause a social disability, in mat they are annoying and cause attention to be drawn to the individual. However, they don't interfere with actions or lead to physical disabilities, as does chorea. Individuals who have significant chorea may fall or drop objects, which can sometimes be confused with ataxia.
Dr. Listernick: How would you classify this girl's movements?
Dr. Goldstein: As they are very stereotypical and repetitive, they sound like tics. Although she's not making any sounds, vocal tics, such as grunts and throat-clearing sounds, are common.
Dr. Listernick: What do we understand about the pathophysiology of tics?
Dr. Goldstein: In reality, not very much. Tics and chorea are disorders of signal outflow from the basal ganglia. Positron emission testing (PET) scans of children with tics are normal.
Dr. Listernick: What is the differential diagnosis of a child with new-onset tics?
Dr. Goldstein: Probably the most common cause is a primary tic disorder. This might be precipitated by exposure to medications, particularly stimulants such as methylphenidate. Certainly, one has to consider Tourette's syndrome. Finally, there's the controversial diagnosis of Pediatric Autoimmune Neuropsychiatrie Disorder Associated with Streptococci (PANDAS).
Dr. Listernick: Let's discuss Tourette's syndrome.
Sharon Hirsch, MD, child psychiatrist: First, we need to confirm that she's really having tics. From a psychiatric viewpoint, obsessions or compulsions can masquerade as tics. A compulsion to wipe a table may be confused with a tic in which someone repeatedly makes a motion with his hand. Can we better define her mood lability?
Dr. Listernick: Her mother stated that her daughter often cried for no apparent reason.
Dr. Hirsch: She might have a concomitant depression or dysthymia. However, it sounds as though the tics are independent of her mood. Tourette's syndrome is a common disorder affecting 1% to 3% of the population. To establish this diagnosis, a child should have a combination of motor and vocal tics that occur for at least a 1-year period. The powers that be decided upon one year of symptoms as a diagnostic criterion so as to distinguish Tourette's syndrome clearly from a simple tic disorder, which generally disappears over several months. The tics do not have to occur at the same time. Often the verbal tics get mistaken for allergies or throat-clearing sounds. Subtle eye blinking may be confused with seizures. Tics cause no physical harm but may be socially disabling. At times, they may be so disabling as to interfere with one's ability to eat or dress oneself.
Dr. Listernick: What are the comorbidities with Tourette's syndrome?
Dr. Hirsch: Attention-deficit/ hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) often coexist with tics in Tourette's syndrome. The combination of two or all three of these disorders can be quite disabling.
Stanford Shulman, MD, pediatric infectious disease physician: How often is coprolalia a part of Tourette's syndrome?
Dr. Hirsch: Although it's the symptom that's most played up in the media, it's actually quite uncommon.
Dr. Listernick: As an aside, one of the best books that I read last year was Motherless Brooklyn, a murder mystery written in the first person, narrated by an orphan growing up in Brooklyn who has Tourette's syndrome. Every now and then, it's nice to cast out a cultural pearl.
Charles Swisher, MD, pediatric neurologist: All too often physicians, seeing a child who has tics, automatically give a label of Tourette's syndrome. Parents hang on these diagnoses, and an inaccurate label can be as devastating as the diagnosis itself. For example, using a label of "epilepsy" in a child who has had one seizure is absolutely wrong. Beyond the chronicity of the symptoms, which is very important, the symptoms must cause a marked distress or significant impairment in social occupation or other important areas of functioning. Children with simple tics generally function well in their community. Children who have Tourette's syndrome often have maladaptive behaviors as a consequence of their tics.
Dr. Hirsch: I agree. However, another way of looking at it is that we see large numbers of children who are mildly affected by Tourette's syndrome. Let's engage these families and help educate the public so as to get rid of the stigma.
Dr. Listernick: When this child was initially seen here, Dr. Swisher ordered an ASO titer and a throat culture for Group A ß-hemolytic streptococci (GABS). Before we discuss the rationale for this testing, were these the correct tests to perform if one is looking for streptococcal disease?
Robert Tanz, MD, general academic pediatrician: In the absence of symptoms, a positive throat culture for GABS indicates that an individual is colonized, an asymptomatic carrier. It's like dirt behind an ear: if you don't look for it, you'll never find it and it won't hurt you.
Dr. Listernick: Try telling my mother that.
Dr. Tanz: If you want to know whether someone has had an antecedent streptococcal infection, you need to send two or more streptococcal antibody titers. Not all GABS infections elicit antibodies to ASO. The other commonly used streptococcal antibody is antiDNAase B. The sensitivity of ASO alone is about 70% and of antiDNAase B alone is 80%; they have a combined sensitivity of close to 95%.
Dr. Listernick: How do you interpret the results?
Dr. Tanz: It may be difficult. As with any other serologic testing, it's most helpful to get acute and convalescent titers. A single elevated ASO titer only tells us that there was a past exposure to GABS. Chronic streptococcal carriers have been reported to have persistently, somewhat elevated ASO titers.
Dr. Listernick: These are total antibody titers. Why aren't there specific IgM titers?
Dr. Shulman: It may be that children only develop an IgM response after their initial GABS infection. There are marked age differences in the normal range of specific streptococcal antibody titers. This nine-year-old child is likely at the peak of her exposure to GABS. Although this child's ASO titer was reported to be elevated at 1 :340, this value is probably well within the expected range for her age.
Dr. Listernick: Why were you looking for evidence of a preceding streptococcal infection?
Dr. Swisher: As she had the rather explosive onset of tics, I was hoping to dispel any future questions about the role of PANDAS as the etiology of her symptoms.
Dr. Listernick: What is PANDAS?
Dr. Shulman: The neuropsychiatrie literature has been flooded with the concept that GABS is responsible for an increase in the number of children diagnosed with tic disorders for the last decade. The typical description of a case of PANDAS is a prepubertal child who has the sudden onset of a tic disorder, OCD, Tourette's syndrome, or any combination of the three. Although I believe that the relationship between the neuropsychiatrie syndromes and GABS is unproved, the proponents of PANDAS have shown that a large number of such children have quasi-elevated levels of streptococcal antibody titers or have GABS isolated from a throat culture at the time of diagnosis. In addition, in some children, the symptoms of the tic disorder tend to wax and wane for a year or more; the pro-PANDAS physicians believe that at least some of these exacerbations are associated with new episodes of streptococcal pharyngitis. Finally, there are some data that serum antineuronai antibodies, as seen in patients who have Sydenham's chorea, exist in some of these patients.
Dr. Listernick: Is there any other hard evidence to prove the existence of PANDAS?
Dr. Shulman: The National Institute of Mental Health blindly randomized children who had a diagnosis of PANDAS to receive a course of penicillin or placebo in an attempt to see if exacerbations of tics could be prevented. The study was inconclusive because of some design flaws. However, the National Institutes of Health recently has funded a large, multicenter, prospective, randomized trial of prophylactic penicillin versus placebo, which hopefully will generate data to either disprove or strengthen the alleged association with GABS. In particular, the treatment period will be sufficiently long so as to encompass the normal fluctuations in a patient's symptoms. My bias is that we may find that there are many different stressors which trigger the exacerbation of symptoms, of which GABS is only one.
Dr. Tanz: There is evidence mat family members of children with PANDAS have a higher rate of OCD and tic disorders suggesting that there are either familial or environmental factors influencing its development.
Dr. Listernick: Where does OCD fit into all of this?
Dr. Hirsch: Individuals who have Tourette's syndrome are at risk for developing OCD. Conversely, children who have OCD have a higher incidence of tics. Whether one believes in the existence of PANDAS or not, there have been trials of antibiotics and plasmapheresis in the treatment of OCD and PANDAS. Unfortunately, there are physicians who routinely treat children who have new-onset OCD or tics with antibiotics.
D. Richard Martini, MD, child psychiatrist: I agree with Dr. Hirsch. I have seen a number of families whose children have OCD and a history of exposure to GABS who insist on receiving antibiotics to treat the OCD. This is an example of the "dark side" of the dissemination of inaccurate information on the Internet.
Alex Bassuk, MD, fellow in pediatric neurology: A recent meta-analysis in Advances in Neurology of the controversial treatment studies of OCD, primarily plasmapheresis and antibiotics, concluded that there was not sufficient data to support the use of either therapy for OCD.
Dr. Listernick: What is OCD?
Dr. Hirsch: Individuals who have obsessive-compulsive disorder have intrusive thoughts or obsessions that take over their lives on a daily basis. For instance, they may think "...step on a crack, break your mother's back" and spend their entire day avoiding cracks in the sidewalk.
Dr. Listernick: Getting back to this patient, how should we treat her tics?
Dr. Swisher: In almost all cases of tics, a large diagnostic evaluation is unnecessary. As previously stated, the importance of detection of an antecedent streptococcal infection is controversial. Assuming the neurologic examination is otherwise normal, magnetic resonance imaging, electroencephalograms, and other expensive tests are not necessary.
Dr. Hirsch: Most children who have a simple tic disorder require no treatment as it is generally self-limited. If the tic is chronic or there are multiple tics, before pharmacotherapy, the most important thing is education. The child, the family, the school, and the patient's friends all need to learn about the disorder. Finally, a variety of drugs have been used for tics including Clonidine, guanfacine, and risperidone. Each has potential side effects.
Dr. Swisher: I started this girl on Clonidine, which improved her tics but made her sleepy. Another neurologist that the family subsequently saw stopped Clonidine and started risperidone. This family has seen a number of consultants looking for clarification regarding her symptoms. Families will often seek other medical opinions when a child has a chronic disease for which there is no definitive treatment.
Dr. Shulman: I'm pleased that this child was not given chronic penicillin prophylaxis. Too many physicians consider PANDAS an analogous situation to Sydenham's chorea and rheumatic fever and treat these children with daily penicillin until they are 21 years of age.
Dr. Listernick: Too much art without enough science. Thank you, everybody.