We have taken questions most frequently asked by parents about OMS from email queries and responses. Here is a directory to the topics of conversation. Click on the topic of interest.
· ACTH
· Behavior problems
· Chemotherapy
· Giving Medications
· Immunizations
· Infections
· IVIG
· Neuroblastoma
· Prognosis
· Psychological
and Educational testing
· Reactions to medications
· Relapse
· School
· Steroids
· "Steroid sparers"
· "Travel Tips"
Q: "What is the difference between ACTH and steroids--concerning the positive effects on the OMS--concerning the negative side effects of such a treatment? Our doctors are very skeptical of ACTH treatment, so they hesitate making a step in this direction."
Comparing the positive effects of ACTH and steroids, ACTH has a higher likelihood of inducing a neurological remission. Both treatments have similar side effects.
Q: "When a child responds relatively well to intermittent steroids and IVIG, do you think it sufficient to go on with this kind of treatment, or would you always advise to give a high dose treatment of ACTH?"
Corticotropin (ACTH) is the gold standard of care in OMS. In our experience, using a high-dose protocol we developed, it is greatly superior to steroids, and can usually induce a neurological remission. Available as ACTHAR gel 80 IU/cc, it is given by intramuscular injection twice daily for one week, then daily for two weeks, then on alternate days thereafter. Intravenous immunoglobulins (IVIG) can be given during the course of ACTH treatments, and many patients will derive synergistic benefit.
Q: "My son had one adrenal gland removed due to neuroblastoma and he now takes ACTH. I read that the adrenal glands produces a steroid that goes to the pituitary gland, then the pituitary gland produces ACTH, which then cycles back to the adrenal gland and starts the cycle all over the balance the body. Have you found any abnormalities of the adrenal gland function in children like him?"
Children with one healthy adrenal gland can do quite well. The doses of ACTH used to treat OMS exceed those produced by the body, so there is plenty of hormone while on therapy. Once ACTH is discontinued, it may be necessary to give a supplemental steroid called hydrocortisone for a while, until the adrenal gland resumes making steroid on its own. This requirement is usually temporary.
Q: "Sometimes my daughter will be seriously mean to her little brother. Several times I've caught her hitting him in the head and laughing as he's crying, running over his legs, feet, or hands with a big wheel and almost enjoying it while he cries. It's unnerving because she'll be smiling all the while with this terrible evil smile. I can understand that she's jealous of him, but how she goes about expressing it is what makes me uncomfortable. Have you experienced this type of behavior with OMS before?"
Yes. It is typical of children with OMS who have behavioral problems. The aggression is directed at family members, particularly siblings. It's important to treat it by modifying the behavior through setting limits and expectations.
Q: "What is the effect of chemotherapy on the OMS? The papers we found are very contradictory on this subject. Is it the removal of the antigen, or is it mostly the immunosuppressive effect of the chemotherapy that helps?"
The role of chemotherapy in the treatment of OMS has not been adequately studied. I have taken care of children with paraneoplastic OMS who did well or poorly despite cancer chemotherapy with cytoxan, adriamycin, or other agents. I am aware of a child at another facility who was treated so aggressively with chemotherapy as to require a bone marrow transplant. So I think one has to be judicious.
Q: "Have you any experiences that the use of chemotherapy correlates
with improved neurological prognosis?"
The current controversy is whether a child such as yours with fully resected neuroblastoma should also receive chemotherapy, not for tumor control, but to destroy the lymphocytes that carry on the autoimmune response. There is a protocol in this country to use cyclophosphamide for that purpose for all children with neuroblastoma in combination with IVIG plus steroids. I can't advise you yet about that without knowing how well she can be made to respond to other measures.
Q: "My child doesn't take oral meds very well. He usually spits them out, or if he is forced, his gag reflex kicks in and it gets ugly. Any suggestions?"
For many medicines, you can mix them in a small portion of applesauce-small enough you know that the child will take it all. Most pharmacies now offer flavors that can be used to cover the taste. Check with your pharmacy.
Immunizations
Q: "I am scared that my child will get Chickenpox. It was suggested
to us that she could have the vaccine after being off of IVIG for 8 months.
We were told that if we know she has been in contact with chicken pox
to bring her in to get the vaccine because it would be better than a full-blown
case. I know that many parents choose not to continue with immunizations
of any kind. What is your advice on this matter?"
We advise giving VZIG when there is a known exposure to chickenpox because chickenpox can cause severe cerebellar ataxia in some childen.
Q: "My daughter is in pre-school until August and then starts Kindergarten in September. Her school is requesting that she is immunized. How do I make that decision or do you just mandate that OMS children shouldn't get immunized?"
It's always a tough call. We make an individual recommendation based on assessment of the risk of relapse and the risk of serious illness. Some of the questions for that assessment are:1) How many times has the child relapsed previously?
2) How many serious infections has the child had?
3) Does he/she relapse consistently with illnesses?
4) Are the symptoms of OMS currently controlled?
5) Is he/she immunosuppressed?No matter how scientific you are about it, it's still a roll of the dice. Certainly,
no live virus vaccines should ever be given and multiple vaccines should not be given at once or in close proximity. Some parents choose to test the water by giving one that's less likely to cause a problem, like HIB, and see how it's tolerated.
Q: "We are going to a wedding and planning to stay with my in-laws. My brother-in-law just called and said he has shingles that is being treated with Valtrex. We are all concerned about our son. Is this something we should keep him isolated from or is it of no concern?"
If your brother-in-law is otherwise a healthy individual (not immunosuppressed), he will not shed virus from his mucosa (nose, throat, etc.). So if your son does not have any physical contact with him, things should be ok. If your brother-in-law's zoster lesions are in an area covered by clothing, so much the better. Here's the important point. If your boy has never had chicken pox before and is getting chemotherapy he is at risk. If it is within 96 hours of exposure, he should get VZIG (a specific type of IVIG). In any event, the incubation time is about 10 days. You should check him for lesions at that time. If he contracts the illness, he may need to be treated with Acyclovir. Again, this only applies if he has NOT had chicken pox.
Q: "My child's case was said to be viral though no specific virus was ever named. She had bronchiolitis 4 months prior to OMS. Do you think there might be a connection?"
The virus that have so far been implicated in OMS are neurotropic viruses, meaning that they can access the brain and cause encephalitis or meningitis. Although almost every child in the U.S. gets bronchiolitis, it is not neurotropic.
Q: "How much IVIG is enough? When we have tried to delay treatment for 1-2 weeks (i.e., go 6-7 weeks between IVIG infusions instead of 4-6), her balance deteriorates, her behavior goes to pot, and we see intermittent myoclonus."
Clinically it seems that she needs the IVIG. I don't know of any IVIG-dependency states--I mean that the IVIG itself causes further need for IVIG. More time may be required before weaning can be attempted.
Q: "Our daughter was started on IVIG treatment last week (she is still taking oral steroids). She was given the treatment over three days. However, over the weekend her symptoms appear to have got a little worse to us - especially the ataxia. Our neurologist here said that the symptoms should not get worse; the IVIG should either help or have no impact. Can you give us any indication from your experiences as to how long it generally takes for the IVIG to take affect (I understand that it varies greatly with different cases)?"
Typically, benefit from IVIG is seen within the first month, even a few weeks. However, 2-3 infusions (one a month) sometimes are required. There may be some transient, mild worsening after the first infusion-usually not. It isn't a reason to discontinue the IVIG.
Q: "We attribute much of my son's improvement to the use of the IVIG at regular intervals, protecting him from potential viruses that cause regression. All of a sudden, after more than six years of paying for the treatment, his primary insurance company is denying payment stating it is 'experimental' and not supported by 'peer medical literature.' What can we do?"
IVIG is not experimental. It is supported by the literature, although the number of articles out is admittedly small. Look on our website under "insurance information" and you'll find a letter of medical necessity for IVIG with references.
Q: "Is complete tumor removal one of the important tenets of OMS treatment? Do you also advise to give chemotherapy if complete surgical removal was not possible?"
Most neuroblastomas associated with OMS are not aggressive, probably due to both host and tumor factors. I imagine that some day we will probably not be removing them. However, the current recommendation is to remove the tumor in the hope of reducing the antigen "burden" on the immune system. Some children improve after surgery; others do not. Tumor removal is seldom an indication to desist in efforts to redirect the immune response. The reason for this is probably memory function of certain T lymphocytes.
Q: "Our doctor will not check for neuroblastoma again unless my daughter relapses. She is 4 years out and has never relapsed. Would this be your plan, too?"
I think that is very reasonable.
Psychological and Educational testing
Q: "I have a question about arranging the neuropsychological
testing you
recommended for children with OMS. I contacted a local psychologist, who
didn't quite know if this was the place I truly needed for testing. How
can
I find out who is the best person in my area?"
Families who are having trouble finding psychologists in their area to do neuropsychological testing can check with the APA (American Psychological Association). The APA may even denote who specializes in neuropsychology. For children under three, the Early Intervention (Zero to Three) system has developmental specialists who perform basic developmental testing. This is nice because it is free of charge to the parents if the child has disabilities, and OMS would certainly qualify.
Q: "Is there a danger that one can miss the right moment to prevent long term damage?"
The exact window of opportunity for treating OMS is unknown. We do know that early and adequate treatment affords the best chance. We aim for full recovery within the first year.
Q: "I know that this is basically a "wait and see" game.
Given the information and the fact that my daughter hasn't relapsed since
diagnosis several years ago, what do you think the chances are that she
may never relapse?"
The chances are good. There are no guarantees. In the extreme, some patients can relapse ten years later, but we don't think this is common.
Q: "In your experience, how quickly should we expect a complete
resolution of the OMS symptoms?"
Resolution of symptoms comes in stages. Response of myoclonus and opsoclonus to high-dose ACTH takes place within days after starting. The improvement builds until it plateaus. Response to IVIG may take a little longer-a week or two-but follows the same general guidelines. Speech improvement takes longer because there are brain developmental issues at play.
A common mistake is to wait months to see a substantial change. In our experience, that indicates a non-responder.
Q: "Our daughter was given Morphine, Benadryl, and Klonapin. She reacted to both Morphine and Benadryl. She had a seizure that lasted 40 minutes after being taken off Klonapin. We want to know if this could have triggered the seizure?"
Seizures are uncommon, but have been reported in children with OMS, so we don't know if the threshold for seizures already was lowered in your daughter due to the OMS. On the other hand, many children with OMS have side effects from drugs like Morphine and Benadryl. We recommend that they not be given these drugs. The small dose that some kids require as a pretreatment for IVIG is probably okay."
Q: "My child is relapsing. He had a stage I neuroblastoma removed and is still being treated with ACTH, IVIG, and cytoxan. On high dose ACTH, he was 100% himself. After about 6 weeks, his doctor was so pleased that he started the weaning process from ACTH. Then the symptoms came back. Now he can't stand alone and is having the same eye jerking as he had before. What can we do?"
The ACTH weaning was too rapid. The dose needs to be raised. If you go back to the initial high dose, I would suggest using alternate day dosing because you otherwise will see more steroid-like side effects. It may take longer to see a response than before. Continue with the other treatments as well.
Q: "We found a very remarkable statement on the Internet: 'Unfortunately the majority of children are left with some degree of learning and/or behavioral disability. There is no evidence that the dose or choice of drugs influence this disappointing outcome in respect of learning or behavior and the reason for this is the subject of significant research.' Do you agree?"
I disagree with the statement because I think it sends the wrong message. It's based on old treatments and bad data. In severe cases, it's true that learning and behavioral problems are frequent, but I think there are some sad and changeable reasons why this is so.
Parents of children with OMS realize how difficult it is to get early recognition and treatment for OMS. It's almost impossible to have it instituted within hours or even days of the onset of the symptoms. So no one has been able to collect data on what I would call early treatment.
As to the dose or choice of agents, there is very little published data on multimodal therapy. Ours is in the works, and others are analyzing their's also. So multimodal therapy (IVIG, ACTH or steroids, cancer chemotherapy or anti-lymphocyte activation agents, plasmapheresis) was not previously used. We now know that single agent therapy is insufficient except in the mildest of cases. The old data is based principally on children treated with single agents. One the whole, many physicians are reluctant to use ACTH and when they do, they use it at low doses.
So I'm worried that that kind of pessimistic statement will cause a relaxed view of treatment and many children with OMS will have a sub-optimal outcome. I have no doubt that better treatments will come, but we will need to institute them sooner, too.
Q: "Our daughter has really had a bad go with her OMS, all this brought on by an influenza virus that struck the whole family about 2 weeks ago. Her cold symptoms are gone but now her eyes are dancing in her head, she has trembling, not wanting to walk sometimes, and more frequent meltdowns with increased severity. She had IVIG 3 weeks ago. Do you have any advice?"
Take her for an IVIG infusion now. I know this is earlier than the usual once monthly dosing, but you can do this as long as it's been at least 2 weeks after the last one. We don't do this for just any infection, but ones associated with relapse.
Q: "A question regarding relapses. My son is doing great, but if he should relapse, what would we see? Would some of his symptoms start slowly coming back, would he crash so to say and look like he did at his worst point, would the eyes just start shaking...what exactly is a telltale sign of a possible relapse?"
Relapse is the return of any symptoms of OMS. How quickly it happens and how severe it gets is very individual matter. The worst relapses are usually seen in kids with serious infections, especially with fever. However, children prone to relapse may do so with almost every viral infection.
School
Q: "Do you have any advice on what we should do about school for
our son? His tutor is concerned that he is going to need a little extra
attention and wanted us to look into schools that have 12 to 15 students.
She says he is doing great, but she can tell when it is time for a treatment.
He has a hard time staying focused unless it is something he is interested
in. She is concerned about a traditional classroom setting working off
a blackboard. She is also concerned about his fine motor skills. First
grade will be a lot of writing and she is concerned about his self-esteem
because he told her the kids were mean to him at his old school. In addition
he needs more time to complete tasks and his writing is not always legible.
I am concerned about his stamina and going to school all day. He still
gets tired if he does too much each day. Do you have any suggestions?"
The specifics from neuropsychological testing will be your best guide. But in general, I think your tutor's recommendations are sound. The guidelines are similar to those for attention deficit disorder, with which the schools are more familiar, and you might make that analogy. In addition, your son should be allowed to use the computer when possible, rather than having evaluations dependent on handwriting. Regarding the fatigue, he may need a shortened school day with home tutoring to cover the rest of the day's material. I recommend counseling for children old enough to perceive their deficits to avoid frustration, anger, and poor self-esteem.
Q: "If we opt to continue with the steroids, would you say that Dexamethasone, Prednisone, or Prednisolone is a better choice?"
If steroids are to be used, we recommend intermittent pulse doses rather than daily dosing. Dexamethasone given for a week at the beginning of each month may give more benefit than other steroids. What you want to avoid is using steroids every day, as that greatly increases side effects.
Q: "Regarding the 'steroid sparers,' I am under the impression that they are different than ACTH and that help in the weaning process. How do the sparers help and what are they?"
It is also important to begin a "steroid saver" about one month after starting ACTH to maintain the neurological remission obtained by the ACTH. Despite a slow 20-week taper of ACTH or steroids, some patients will relapse unless they are also taking a steroid sparer. Azathioprine can be used at 3-5 mg/kg/day. Other steroid sparers are available, too. The use of these agents does not cause tumor regrowth.
Q: "If you keep trying to wean from ACTH and you have problems,
does that mean the harmful cells are cloning over and over again and don't
ever die off?"
During the first year after the appearance of OMS, we assume that's the case, and give additional immunotherapy. The studies on lymphocytes we do help look into that problem. I wouldn't say that they will never die off, especially as our treatments improve.
Q: "We're planning to go on vacation, but my child is several medications for OMS. What special precautions should we take?"
There are no absolute restrictions. We do have a few suggestions to consider while traveling:
Print off our website and tuck away in a purse the "List of Medications
To Avoid," should your child become ill and need to be seen in an emergency
room.If your child does come down with a fever, take along some children's
Tylenol, give dose as directed for child's age to keep the fever down, offer an
easy diet, and push the fluids.Best to keep away from people who are actively ill with a fever, head cold, or flu symptoms.
At family get-togethers, avoid passing around your OMS child too much for
the required hugs/kisses! ACTH and chemotherapy suppress
the immune system and leave the child more vulnerable to infection. You never
know who is harboring a summer virus.Bottom line: just use common sense. Have a great vacation and enjoy yourselves; you all deserve it! :-)
