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School-Related Medical Issues Archive 2014

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John L. Digges, MD, PhD, MPH, FAAP
(Fellow of the American Academy of Pediatrics)
Behavioral Pediatrician

Dr. Digges practiced general and behavioral pediatrics in Oklahoma and California for 14 years. For ten of the past 12 years, he has served as the Forensic (Child Abuse) Pediatrician for Kern County, California; and he has had a private practice limited to ADHD consultations for the past 12 years. He has been a CME surveyor for the Institute of Medical Quality (CMA) since 2000, and is a recent past-President of the Kern County Medical Society. Dr. Digges has been at the DCN since August, 2008.

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  • Treatments for Students with Complex Profiles

Question:

Dear Dr. Digges,

My son is an 8th grade student, who is fully included in general education classes. He had a previous diagnosis of Asperger Syndrome but now is considered an individual with ASD who is high functioning.

He was 14 years old in December and like many people with Autism, has difficulty with focus (ADHD), anxiety, depression and obsessive behavior. In the past two years my son has developed vocal and physical tics that have resulted in the diagnosis of Tourette Syndrome.

Over the past 10 years my son has received a variety of educational interventions as well as combinations of medications to support his ability to access the curriculum in the general education class.

I have worked closely with his doctors over the years, monitoring dosage and combinations of medications to address attention, focus, anxiety, depression and recently the symptoms due to Tourette Syndrome. I am very concerned that medication my son has and is taking may not be the most effective and I am concerned and desire to minimize negative side effects, while maximizing positive effects.

It is for this reason I am asking your help in clarifying: “What medications/treatments are currently effective for people with a similar profile as my son?” (i.e., Asperger, anxiety, ADHD, depression and Tourette Syndrome)

As you can see, my son is a complex individual, with many of the challenges that accompany ASD emerging full blown this year with a high intensity and frequency, resulting in extreme stress and anxiety for him.

Current medications include:

Concerta at 36mg. since 9/2014 (over the summer, he was taken off this medication)

Prozac 20 mg. at night

Previcid 30mg in the morning

Tenex 10/16/14. 1 mg in the morning and 2 mg at night since November

We look forward to any help or insight you can provide.


Answer:

Thank you for your questions. Your son’s complex constellation of symptoms has resulted in his having received multiple diagnoses and medications. This is understandable, but some degree of confusion is bound to occur in such a complicated condition. My goal is to offer some comments which I hope will be helpful for you, your son, and his treatment team.

Your son’s physician has taken a sound approach to treatment. As a general rule, we try to identify the symptom complex which is causing the most difficulty, and then, introduce a therapeutic intervention to address those symptoms. This may entail titrating a medication from a low dose to higher doses gradually over time, while monitoring for both symptom reduction and the onset of any undesirable side effects. Since medications always have side effects, it is not a matter of avoiding side effects entirely, but rather keeping them within an acceptable range.

After observing a significant reduction in the first symptom complex, we re-assess the child to determine what other symptoms remain. These persisting symptoms may require a second intervention or medication, which we again add cautiously; titrating the dose upwards to attain maximum symptom reduction without causing unacceptable side effects. I try to avoid treating side effects introduced by one medication with another medication, and instead attempt to see if a reduction in dosage results in a decrease in the side effects to an acceptable level. I can then choose a second medication with a different side effect profile to see if we can attain additional symptom reduction without producing unacceptable side effects.

The use of medications to treat complex clusters of symptoms will always be fraught with challenges. A medication used to treat one set of symptoms (e.g. a stimulant medication for ADHD) may have side effects (e.g. increase in irritability and anxiety) that pose great challenges in some children (e.g. coexisting autism or anxiety disorder). The medications themselves may interact, in that one medication might alter the rate at which another medication is metabolized, making its blood level potentially either higher or lower than it was before the second medication was added. Clearly, medication management will consist of a lot of “trial and error” and will be a true “team effort,” with adjustments made on the basis of feedback provided to the clinician from the patient and the patient’s family.

Vyvanse 20mg is a relatively low dose long acting stimulant preparation. It appears that an increase to 30 mg resulted in improved focus for an extended period of time. Prevacid was started about a year after he had been taking the Vyvanse, due to concern about acid reflux affecting his teeth. One possible interaction between Vyvanse and Prevacid is the potential for slowing the absorption of each medication. (Interestingly, the Prozac he was taking at that time has the effect of increasing the blood level of Prevacid, which might offer an explanation as to why the Previcid continued to be effective). One report of a small study monitoring 26 patients taking both Vyvanse and Prevacid listed “drug ineffective” as one of the consequences noted in 10-19 year old males.

A possible explanation for this involves the particular system for delivering dex-amphetamine which is present in Vyvanse. The molecule ingested is a “pro-drug,” consisting of an l-lysine molecule which has been attached to the active dex-amphetamine molecule. The bond is cleaved by enzymatic activity occurring in red blood cells in the small intestine. Although changes in pH did not appear to affect the release of dex-amphetamine in test tube studies, it is at least possible (although it has not yet been demonstrated) that the increase in pH associated with the use of Prevacid might interfere with enzymatic cleavage of the l-lysine molecule in red blood cells perfusing the small intestine in at least some male patients. A trial of Adderall XR (dex-amphetamine salts without a prodrug release mechanism) might help to determine whether the molecule or the release mechanism is the problem.

Your son has more recently been taking Concerta (OROS d,l-methylphenidate), having been titrated from 18 to 27 and then to 36 mg. He reportedly experienced improved concentration initially, but a loss of focus the last portion of the school day. One possibility that should be explored is that the medicine he was prescribed (“Concerta”) may not have been the medicine he was administered.

During 2014, Concerta was available as a brand name and as a generic manufactured by Actavis (previously Watson). These medications are identical (elongated tablets with a laser drilled hole at one end and “ALZA” imprinted on the tablet), and both employ the OROS release mechanism, which results in a prolonged upslope of the pharmacokinetic curve. This prolonged upslope appears to be crucial in enabling students to benefit from improved focus for 6-9 hours. Unfortunately, the FDA was also allowing 2 companies which produced non-OROS “sustained release” preparations of d,l-methylphenidate to market their products as “biologically equivalent” generics for “Concerta.” The molecule is equivalent, but the release mechanism is not. These two generics, like the brand name Ritalin-SR product, produce a 1-2 hour upslope, followed by a 5-7 hour plateau. Since the beneficial effects on attention are correlated with upslope of the curve, one would expect poorer attention to be demonstrated by students after the first couple of hours on the latter preparations. If your son was given a generic for “Concerta,” it may have been one of the non-OROS preparations. If so, then a trial of d,l-methylphenidate which employs the OROS release mechanism may prove beneficial.

Another option would be to try a formulation of dex-methylphenidate (trade name Focalin XR), while observing for both a reduction in ADHD symptoms and the onset of possible side effects in response to this medication. Titration of the dose can be done more precisely than with Concerta. Although this is typically not much of a concern, it may well be significant for a student with ASD, as this population tends to be more sensitive to side effects of stimulant medications.

The increase in tic behaviors while off of Concerta during the summer of 2014 is noteworthy. Reports in the literature suggest that although many children with tics experience an increase on stimulants; others see no change, and a few experience a dramatic decrease in tic frequency. Clearly, there are other factors at work than just the presence or absence of stimulant medication.

Tourette Syndrome (TS) is diagnosed when a person displays multiple motor tics and at least one vocal tic for more than one year. Since tics are often noted to increase during times of stress, identifying potentially stress inducing situations and developing strategies to minimize them is an essential step in reducing tic severity and frequency. Therapeutic efforts to decrease both stress and tics can include CBT (Cognitive Behavioral Therapy) and CBIT (Comprehensive Behavioral Interventions for Tics). CBT has been successful in patients with anxiety disorders, so might well benefit your son by reducing his levels of anxiety and stress. CBIT is tailored more specifically to tic reduction, and involves learning to recognize the earliest indication that a tic is about to occur, and then engaging immediately in a “competing response” behavior. With this approach, it is felt that increasing the individual’s awareness of their condition helps them to feel more relaxed, empowered, and self-confident; and thereby contributes to a reduction in tic severity and frequency.

Additionally, as a child’s ADHD symptoms are reduced with stimulant medication, their overall degree of frustration and stress is also reduced. This reduction in stress may contribute to a reduction in severity and frequency of tics. Another consideration regarding his increased tic activity while off of stimulants during the summer is that your son was on Prozac 20 mg and Prevacid 30 mg during this period. Prozac can interfere with the metabolism of Prevacid, resulting in an increase in the level of Prevacid in the blood. One of the side effects reported with Previcid after more than one year of usage is hypomagnesemia, which can produce jitteriness, jerking movements or tremors. This might conceivably contribute to an increase in apparent or actual tic activity. It therefore might be reasonable to check a magnesium level in your son, and provide supplementation if indicated.

When medications are used to treat tics, especially in a patient with executive function deficits, Tenex (guanfacine) is a reasonable choice. A longer acting version called Intuniv is also available in strengths of 1-4 mg. This medication has shown efficacy in reducing both tics and executive function deficits as well. Its main side effect is sedation, which tends to decrease over time. By reducing some of the executive function deficits, it may also allow for using a decreased dose of stimulant.

The combination of methylphenidate (e.g. Concerta or Focalin) and Prozac decreases the metabolism of the Prozac, causing its effects to be increased. This can be helpful for a child with anxiety, as the dose of Prozac, which is needed to effectively manage anxiety, is significantly higher than that needed to manage the symptoms of depression.

Your son has a particularly challenging combination of symptoms, and giving him optimal help will require diligence. The potential for both side effects and drug interactions is significant. However, there are opportunities for reducing the intensity and frequency of those adverse events and interactions, and I hope my comments will provide some help.

Thanks again for your question.

John L. Digges, MD, PhD, MPH, FAAP

Behavioral Pediatrician at the Diagnostic Center North, Fremont, California


  • Maternal Uniparental disomy of chromosome 14

Question:

I am a speech therapist in northern California, and I have just inherited a student (aged 8-6) with Maternal Uniparental disomy of chromosome 14. I met her once before when she was 5 and a Huge progress has been noted, but she is now my responsibility, and I need to get information about how the mechanism of her disability is driving her severe lack of intelligibility. It is clear that the muscle coordination and sequencing, and possibly muscle capacity is limiting her ability to articulate, but I find there is very little pattern to her 'mistakes'. She does not present at all like a Childhood Apraxia of Speech, nor is it Ataxic or dysarthric in profile, and it is clearly not an aphasic-issue as she is receptively intact. ... I think! Would this be akin to CP???

I would appreciate any insight into understanding how this problem is driving her inability to access the articulatory positions/patterns and specificity. Motivation is NOT a problem!

She is currently under care for Endocrinology as well as Gastro-Enterology, and has in the past been under the care of Genetics and Neurology.

And she has a delightful spirit, as well as a few other medical problems, which I see as non-related.

Your reply will be anticipated with bated breath as she will soon be due for her Triennial!

With appreciation,
Y W
MA SLP. CCC


Answer:

I was unable to find any literature that would provide a definitive answer to your question concerning the mechanism of speech problems in an 8 year old girl previously diagnosed with maternal uniparental disomy of chromosome 14 (matUPD14). Uniparental disomy occurs when, instead of a chromosome being composed of one paternal and one maternal homologue, both homologues came from the same parent.

Interphase refers to the period preceding meiosis (a particular type of cell division), during which the DNA replicates and homologous chromosomes exchange genetic information. This is followed by meiosis I, resulting in two daughter cells, each containing two diploid cells. Each of the diploid daughter cells then undergoes meiosis II, spitting into two haploid gametes (either an egg or a sperm cell). When an egg and sperm cell fuse during fertilization, a diploid cell is produced with a complete set of 23 paired chromosomes (22 autosomes and 2 sex chromosomes, i.e. either “xx” or “xy”).

Rarely during meiosis, the diploid cell does not divide (“non-disjunction”), and then there will be a diploid cell (usually an oocyte) and a “nullisomic” cell, each of which can subsequently fuse with a haploid sperm cell. When a diploid egg fuses with a haploid sperm cell, the resulting trisomic cell can convert to a diploid cell by losing one homologue, while the unisomic cell can duplicate to form a diploid cell. In the case of a trisomic cell which discards a homologue from the mother, then the remaining two homologues were from both parents, and this is referred to as “biparental.” If the discarded cell came from the father, then the remaining two both came from the mother, and this is referred to as “maternal uniparental disomy.” When this sequence occurs involving the long arm of the 14th chromosome, it is referred to as “maternal uniparental disomy of chromosome 14.”

This condition of having both homologues deriving from the same parent is rare, and most of these have no consequences for the health of the individual. Chromosome 14 is, however, one of the five chromosomes that have so far been identified which can cause significant alterations in function. Children with matUPD14 can have a range of phenotypic expression. Characteristic findings include intrauterine growth restriction and slowed growth postnatally, hypotonia, laxity of joints, motor delay, speech delay, mild to moderate intellectual disability, precocious puberty, and minor dysmorphic features involving the face. Although I could not find in the literature any specific reference to the types of speech delay or the suspected mechanisms, it may be speculated that a particular combination of slowed growth in the regions of brain responsible for language development, poor motor function involving muscles necessary for speech production, decreased muscle tone in those same muscles, and intellectual disability may contribute to the challenges your student faces.

John L. Digges, MD, PhD, FAAP
Behavioral Pediatrician
Diagnostic Center North, Fremont CA