Myoclonic-Astatic Epilepsy in Ea

Steroid therapy for epilepsy management is considered unconventional and certainly not a decision to be made lightly because of the serious risks and undesirable but common side effects. A child can undergo steroid therapy for only a limited period of time; he/she cannot remain on steroids forever. Unless the epilepsy remits within the course of treatment, steroid therapy will need to be followed with an alternative anti-epileptic drug/treatment (AED) once the steroids are stopped.

How and why steroids work to control epilepsy is poorly understood. Specialists assume it has a useful anti-inflammatory action but it is probable that the release of particular hormones (stress hormone) and their effect on the brain's cortisol receptors and stimulation of the adrenal glands is thought to be beneficial too. One thing is known, steroids can seem like a wonder drug when other treatments have failed.

Even though it can be a wonder drug for controlling seizures, some treating doctors will still refuse to prescribe steroids because they believe the side effects are potentially too harmful compared to other AED (anti-epileptic medications). Yet this treatment option is gaining popularity because doctors are constantly learning safer methods to administer the drug (see pulse therapy with oral steroids). In addition, doctors are becoming more confident in prescribing steroids because studies on their use in chronic childhood illnesses such as asthma have revealed that long-term steroid therapy is actually safer than previously perceived.

Steroids can have an excellent broad spectrum effect for the seizures associated with MAE. Indeed, children with MAE have responded extremely well when other drugs have failed. Steroid therapy might be explored after the main broad-spectrum medications/treatments have failed but probably not before.

There are two main types of steroid therapy used in the treatment of MAE; ACTH which is injected over a short period (usually 8 weeks) and prednisolone (or prednisone) which is taken orally for a longer term.

These types of medicines are simply called steroids, but it should be noted that they are very different from another group of steroids, called anabolic steroids, which have gained notoriety because of their abuse by some athletes and body builders.

Andrenocorticotrophic hormone (ACTH) is a first-line treatment for infantile spasms and it can be used in other childhood epilepsies including Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and MAE. ACTH is a peptide hormone produced in the anterior pituitary gland that is administered by injection.

ACTH therapy has caused fatalities and serious complications in the past so it is regarded as a high-risk treatment and used only when it is judged that the benefits (seizure control) outweigh the risks. A good example of this is the use of ACTH in the treatment of infantile spasms.

Because of the known risks, some specialists refuse to prescribe ACTH and opt for a safer approach with oral steroid therapy. Compared to oral steroids, ACTH can be thought of as a super steroid. Some specialists believe that ACTH is superior and more powerful than oral steroid and for some children it might just be the "magic bullet". In this case, the specialist/s and parents may feel that the benefits of treatment outweigh the risks and decide to embark on a course of ACTH in preference to oral steroids. Whereas other specialists believe that oral steroids will provide the same results although it might take longer to start working, and choose this safer option.

Typically for the treatment of uncontrolled epilepsies in children, the drug is administrated by injection daily for approximately 4 weeks and then tapered over the next 4 weeks. The most common adverse reaction is hypersensitivity – an allergic reaction – in which case treatment will be abandoned. As ACTH therapy takes place over a short period, an alternative anti-epileptic drug/treatment will probably be established to follow on from treatment. If a child has responded well to treatment and the steroid has been well tolerated, ACTH might be followed by oral steroids (prednisone or prednisolone) over a longer course.

There are two forms of ACTH; the natural form and synthetic (man-made) form. The most commonly administered form of ACTH is the synthetic form for several reasons. Apart from the fact that it is much easier to source and cheaper to prescribe, the synthetic formula ensures a precise dose measurement with a slow-release action which deems it safer to use that the natural form. However, some specialists (and parents!) believe that the natural form of ACTH is superior and they may insist on using the natural form because, as in Will's experience, it might just be the "magic bullet" and stop the seizures for good.

Because of the high risks associated with ACTH, specialists often opt for oral steroids – prednisone or prednisolone – which are considered to be much safer. Specialists have had decades of experience with this type of medicine especially in the management of chronic asthma in paediatric patients, and they have learned methods of administration which can minimise side effects significantly. See pulse therapy with oral steroids.

Prednisilone and prednisone (also known as hydrocortisones) are an oral, synthetic type of medicine known as corticosteroids. (Corticosteroids are hormones produced naturally by the adrenal glands located adjacent to the kidneys which have many important functions on every organ system.) These synthetic corticosteroids mimic the action of cortisol (hydrocortisone), the naturally-occurring corticosteroid.

There is a distinction between prednisone and prednisolone. Prednisone is inactive in the body and, in order to be effective, first must be converted to prednisolone by enzymes in the liver. Some specialists favour the use of prednisolone because it can be just as effective as prednisone but may have fewer or less side effects.

Specialists are learning more and more about the safety and long-term side effects of steroids through studies in other chronic illnesses, especially asthma. Specialists have discovered methods of prolonging the useability of steroids whilst minimising the side effects. This means patients can stay on steroids for longer periods of time than previously thought possible using a method known as pulse therapy.

Pulse therapy involves giving the dose every other day or, even better, every 3-4 days (if, that is, seizure control can be maintained between dosing). By giving the steroid every other day instead of every day, the side effects may be reduced by more than 50%. Better still, pulsing twice a week (or every 3-4 days) means the side effects may be negligible. Trialling pulse therapy to establish the safest load of steroid whilst maintaining seizure control means that steroids can be used much longer term in epilepsy management; perhaps one, two or even three or more years.

For the treatment of severe epilepsy, steroids are usually initiated at the highest acceptable dose per kg on a daily basis, given in the morning. Once seizure control is established, the steroids are gradually reduced and at some stage – as determined by treating specialists – the switch is made to a pulse therapy schedule. The aim is to achieve seizure control with as many days between dosing as possible, and on the lowest dose possible. If a trial to pulse every 3-4 day fails, then the patient may attempt alternate day dosing (still highly preferable to daily dosing). Pulsing every 3-4 days is not always successful but, given the benefits, it is certainly worth trialling.

When steroids fail
As with all medication/treatment trials, sometimes steroid therapy simply does not work to control the seizures or it can even exacerbate the seizures. See paradoxical seizure reaction to steroids. At least it can be crossed off the list or attempted at a later stage.

Side effects of of long-term or high dose steroid therapy
These side effects are common but are dose related, ie, side effects increase with higher doses. They are reduced significantly with any form of pulse therapy (be it alternate day or, better still, twice weekly dosing):

All of these side effects are temporary and will go away once the steroid is stopped: growth should resume and catch up, excess body weight and hair will fall away, and the immune system will return to normal, etc. Some of these side effects may be prevented; calcium supplementation may assist bone density, an antacid such as Zantac may help prevent stomach ulcers, and increased fibre intake should alleviate constipation.

There are some dangerous risks associated with long-term or high dose steroid therapy which are reduced significantly with pulse therapy. Some risks are more serious than others.

Not all of these risks are easily reversed or remedied. For example, cataracts can be removed surgically but, in a child, it is not the simple procedure that it is for an adult. Any bone thinning can be improved with supplementation but severe loss of bone density is obviously undesirable.

Steroid therapy requires careful supervision by your treating neurologist, ideally, together with an endocrinologist paediatrician who specialises in bones, growth, hormones, etc, and is experienced in steroid management. This specialist will look for warning signs of any of the serious risks which may develop with long-term or high dose steroid therapy. This will involve mapping your child's growth and weight, taking regular blood pressure readings, occasional blood testing. The specialist may want to test bone density and arrange eye examinations for cataracts, first of all to establish a baseline and follow-up regularly to monitor any change. Nutrition and eating habits whilst on long-term oral steroids must be also be monitored.

Steroids may help control seizures and improve an EEG, however it has been noted that in some patients they can aggravate convulsive generalised seizures, specifically tonic clonic seizures. Parents should be aware that it is possible that steroid therapy could make tonic-clonic seizures occur or, if they are already a feature of the disorder, increase in severity/intensity.¨

Myoclonic-Astatic Epilepsy in Early Childhood (MAE)

(Doose Syndrome)