Juvenile-HD

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SECTION 1 - AT RISK
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-Read If Your Child Is On Antidepressant
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SECTION 8 - MEDICATIONS
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-EPA~Fish Oil
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SECTION 9 - SURGERIES
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SECTION 11- ALCOHOL/DRUGS
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SECTION 16 - EMOTIONAL ISSUES
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SECTION 17 - GRIEF
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SECTION 21 - BENEFITS/INSURNACE
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SECTION 22 - ARTICLES/JHD
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SECTION 23 - CAREGIVING
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SECTION 24 - BIO
Our Personal Experience
Coping At The End
Kelly E. Miller
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Letter From My Heart
GUESTBOOK
Medications-Movement Disorders

INDEX Page

Treatments
 
 
Medication

The following descriptions of medications are intended as summaries and excerpts from the complete available information and are provided for general information purposes only. Not all side effects, complications, or potential drug interactions are listed. In particular, on initial use of after prolonged exposure any medication can cause a severe allergic reaction or other unexpected side effects. Many of these medicines have not been approved by the FDA for use in children. The information here is therefore not to be considered a complete description, and additional information should be sought before making decisions regarding medications. These medicines should be given only with the advice and knowledge of the child's doctor.

Anti-epileptics

Anti-epileptic medications are designed for the prevention of seizures. Nevertheless, this class of medications has also shown benefit in psychiatric disorders and movement disorders. Examples of anti-epileptic medications used for movement disorders include (US trade names are in parentheses):

  • Carbamazepine (Tegretol). This medicine is often remarkably effective for paroxysmal kinesogenic choreoathetosis (PKC). Very low doses are often sufficient to treat the disorder completely. Carbamazepine may worsen myoclonus and myoclonic epilepsy. While the dose is being increased, side effects include nausea and mild sedation. Carbamazepine may cause a decrease in the white blood cell count (WBC) and increases in markers for liver disease.

  • Valproate (Depakote). Valproic acid enhances activity at the inhibitory GABA receptors in the brain's basal ganglia. This is the reason that valproate is helpful for movement disorders. It is often used for myoclonus or chorea. Valproate has a very low rate of side effects in children over 2 years; however, it may cause liver problems, particularly in children with metabolic disorders, or a drop in the white blood cell or platelet counts. Valproate may lower carnitine levels; this usually does not cause problems unless there is an underlying deficiency of carnitine.

  • Lamotrigine (Lamictal). There have been anecdotal reports of improvement in myoclonus with this medicine. Lamotrigine must be increased slowly, and when combined with valproate, there have been reports of life-threatening skin rashes.

  • Levetiracetam (Keppra). This medicine, which is not available in the US, is closely related to piracetam. It has been reported to be an effective treatment for myoclonus.

  • Primidone (Mysoline). Primidone is metabolized to several intermediate drugs, including phenobarbital. It acts similarly to phenobarbital by potentiating activity at the inhibitory GABA synapses. Primidone is useful for certain types of tremor. Side effects include drowsiness.

  • Benzodiazepines. This is a large class of drugs that act on the central nervous system. These drugs include clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), and clobazam (Frisium, not available in the US). All these medications stimulate inhibitory GABA activity; they may be active in the cortex, basal ganglia, and spinal cord. The differences between the different drugs relate to the duration of action and the relative effect on spinal cord receptors. Diazepam is often used for spasticity, while clonazepam is often used for chorea or myoclonus. Side effects include drowsiness and increased oral secretions (particularly evident with clonazepam).
Trihexyphenidyl (Artane)

Trihexyphenidyl is the most effective medication to treat dystonia of unknown cause. It is an anticholinergic medicine, meaning that it acts to block acetylcholine receptors in the brain. Its action is similar to that of diphenhydramine (Benadryl) and other over-the-counter cold/allergy medicines. Trihexyphenidyl's effect on the brain seems to be more specific. Side effects include dry mouth, blurred vision, constipation, urinary retention, and rapid heart rate. These side effects are usually much less frequent in children than adults; therefore children tolerate much higher doses; in some cases, the dose may be as high as 100 mg per day, or even higher. Extremely high doses are often required to see a benefit and it can take a long time to increase the dose to this level. If side effects are bothersome, the blurred vision may be controlled with pilocarpine eye drops; urinary retention can be controlled with bethanechol.

Baclofen

Baclofen (Lioresal) activates the GABA type B receptors that are found in the spinal cord. As a result, it is particularly useful in spasticity. Baclofen can be administered by mouth, but it may also be given by continuous pump infusion into the spinal cord. This is delivered through a plastic catheter, which is inserted by a surgeon. The baclofen pump reduces the side effects, which are primarily drowsiness. Like trihexyphenidyl, baclofen often must be taken in large doses; the dose must be slowly increased in order to minimize side effects.

Dantrolene

Dantrolene (Dantrium) is a direct muscle relaxant that blocks calcium from signaling muscles to contract. It is occasionally used in children with severe spasticity, usually in combination with baclofen or other medications. In some cases, dantrolene has been reported to be useful for hospitalized children who experience brief episodes of very severe dystonic spasms. Dantrolene is also used to treat malignant hyperthermia, a rare but dangerous side effect of anesthesia, and neuroleptic malignant syndrome, a rare but dangerous complication of neuroleptic medications.

Over a long period of time, dantrolene may cause a change in the muscle fiber type to more rapid fatiguing fibers. It may also cause gastrointestinal or liver disease, in addition to mild drowsiness and nausea.

Dopamine and Dopamine Agonists

Dopamine is a neurotransmitter that is used in all areas of the brain. It is particularly important for regulating the function of the basal ganglia. There are at least five subtypes of dopamine receptors, called D1 through D5; the D1 and D5 subtypes are referred to as "D1-like," while D2, D3, and D4 are referred to as "D2-like." These are grouped in its manner because of the common properties of the receptor effects. In children, dopaminergic medicines are used to treat primary deficiencies of the dopamine system, as in dopa-responsive dystonia or juvenile Parkinson's disease. Certain medications may also be useful for tic disorders or static basal ganglia injury.

  • L-dopa/carbidopa (Sinemet and others). If dopamine is taken by mouth, it is rapidly degraded in the intestine and blood and it does not penetrate from the blood into the brain. Therefore, the precursor L-dopa is administered, instead of dopamine. L-dopa is converted to dopamine in blood and in the brain. In order to maximize the effectiveness of L-dopa, it is usually given in combination with a medicine such as carbidopa, which blocks the conversion of L-dopa to dopamine in the blood. Therefore, more L-dopa is transported into the brain, where it is converted to dopamine. The combination of L-dopa and carbidopa is sold in the US under the trade name Sinemet, among others. L-dopa/carbidopa is the primary treatment for dopa-responsive dystonia (DRD) and juvenile Parkinson's disease. There is also evidence that it may be helpful in some children with cerebral palsy. The side effects of L-dopa include nausea, constipation, and low blood pressure. These side effects are often be controlled by the use of additional carbidopa, domperidone (not available in the US), or other anti-emetic medications. L-dopa is absorbed more rapidly with sugar, and less rapidly with protein. In general, the therapeutic effect and side effects are greatest when it is taken on an empty stomach.

  • Dopamine Agonists (Parlodel, Permax, Mirapex, Requip). Another class of medicines called "dopamine agonists" act similarly to dopamine by directly activating the dopamine receptor. Different agonists have varying activities at the different dopamine receptors; therefore, their effects are subtly different. Dopamine agonists have been very successful in the treatment of adults with Parkinson's disease, but there is less experience with their use in children. Certain rare metabolic diseases may respond to treatment with agonists. In addition, there are a few reports of success with treating tic disorders. Available dopamine agonists include: bromocriptine (Parlodel); pergolide (Permax); pramipexole (Mirapex); and ropinirole (Requip). Side effects are similar to L-dopa, with nausea being the most bothersome. There may also be behavioral changes and occasionally hallucinations.

  • COMT Inhibitors (Comtan, Tasmar). A recent class of medications called COMT inhibitors acts by slowing the breakdown of dopamine in the brain. The currently available COMT inhibitor is entacapone (Comtan). Entacapone prolongs the effectiveness of dopamine and may help to smooth out some of the fluctuations seen as side effects from taking L-dopa and carbidopa. It is used primarily for adult Parkinson's disease. The side effects of this medication have not yet been reported in detail, but concern remains due to the fact that a similar previous medication (i.e., tolcapone [Tasmar]) caused severe liver disease in a few adults.

  • Amantadine is a medicine that was originally intended as an antiviral agent. Subsequently, it was found to have effects similar to dopamine. It probably acts by increasing dopaminergic transmission, as well as blocking glutamate receptors in the caudate and putamen of the globus pallidus. There is very little experience with this medication in children; however, reports suggest benefit for dopa-responsive dystonia (DRD) as well as in some cases of cerebellar disease. Side effects are primarily due to nausea. Behavioral changes have been reported as well as mild anticholinergic effects (similar to trihexyphenidyl).

Neuroleptics

Neuroleptics are a class of medications that were originally developed to treat psychosis. Neuroleptics work by blocking dopamine D2-like receptors. This action is thought to have a potentiating effect on the indirect pathway of basal ganglia transmission, thereby inhibiting excess activity in the cortex. Different neuroleptics have different effects on subclasses of the D2-like receptors. This probably explains  their slightly different actions and side effects.

Because neuroleptics stimulate the relatively inhibitory indirect pathway, these drugs are also used to treat disorders of excess involuntary movement. In particular, neuroleptics are very helpful for tic disorders, and occasionally helpful in chorea. They can also be used to treat nausea, psychosis, hallucinations, or behavioral changes caused by L-dopa or dopamine agonists.

Pimozide (Orap) and haloperidol (Haldol) are the two most commonly used neuroleptics for tics in children. Other commonly used neuroleptics include thioridazine (Mellaril) and fluphenazine (Prolixin).

Newer, "atypical" neuroleptics may have a decreased rate of neurological side effects, including clozapine (Clozaril), risperidone (Risperdal), quetiapine (Seroquel), and olanzapine (Zyprexa).

The side effects of neuroleptics can be very serious and they do not always resolve following discontinuation of the medication. In particular, all neuroleptics, with the exception (thus far) of clozapine have been reported to induce parkinsonism and tardive symptoms, including tardive dyskinesia and tardive dystonia. "Tardive" refers to the late occurrence of symptoms, often many months after starting the medicine, and, in some cases, many months after stopping the medicine.

Tardive dyskinesia, a "rabbit-like" movement of the mouth and lower face, and tardive dystonia are difficult to treat and often do not resolve once started. Neuroleptics may also cause an acute dystonic reaction, which occurs when starting the medication for the first time or increasing the dose. In an acute dystonic reaction, the neck or the back arches involuntarily, and the mouth, tongue, and face may be pulled to one side or have continuous rolling or writhing movements. Acute dystonic reactions are usually easily treated with an intravenous injection of diphenhydramine (Benadryl).

Neuroleptic malignant syndrome, characterized by confusion, stiffening of the muscles, high temperature, and elevated muscle enzymes in the blood, is a rare, potentially life-threatening complication of neuroleptic treatment. This syndrome is more likely to occur if neuroleptics are suddenly discontinued. Therefore, it is important to taper the dose gradually before stopping any neuroleptic.

Although clozapine may have fewer neurological side effects than other neuroleptics, it may cause a life-threatening decrease in the white blood cell count. During treatment with clozapine, blood tests need to be taken on a weekly basis.

Tetrabenazine and Reserpine

Tetrabenazine (Nitoman, not available in the US) and reserpine act by depleting the supply of dopamine, norepinephrine, and serotonin in nerve terminals, thereby decreasing the amount available for release. Tetrabenazine may also block both D1 and D2 receptors. These medicines are sometimes useful in dystonia, but reserved for severe cases due to the high rate of side effects.

Tetrabenazine has also been reported to be useful in chorea and tic disorders. In addition, tetrabenazine has many of the beneficial effects of neuroleptics, without causing tardive dyskinesia.

Both tetrabenazine and reserpine may cause parkinsonism; signs of parkinsonism must be carefully watched for, since mild parkinsonian bradykinesia may be difficult to detect in a child with generalized dystonia.

Both medications may cause a decrease in blood pressure (hypotension). This effect is particularly profound with reserpine; in children, this medication must usually be started while in the hospital under frequent blood pressure monitoring. Tetrabenazine may cause drowsiness and, in rare cases, neuroleptic malignant syndrome.

Clonidine

Clonidine (Catapres) was originally developed as a medicine to treat high blood pressure. Subsequently, it was found to be useful for treating childhood behavioral disorders, including attention deficit disorder (ADD), and attention deficit hyperactivity disorder (ADHD), and tics. Although clonidine is not always as effective for treating tics, as are the neuroleptics, the side effects of clonidine are much less serious. Therefore, this medication is often attempted first. Clonidine is available as pills or a patch for a more continuous administration through the skin. The major side effects are drowsiness and dizziness, and in some children, it may cause a drop in blood pressure.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors are a class of medications used primarily to treat psychiatric disorders, including depression and obsessive-compulsive syndromes, and others. Occasionally, SSRIs are also useful for tic disorders and stereotypies. In addition, some metabolic disorders that affect serotonin have benefit from the use of these medicines. The most common of these medications include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa).

These medicines have occasionally been reported to cause chorea or tics. When SSRIs are taken in combination with other types of antidepressants or migraine medications, it is important to watch for the serious "serotonin syndrome."

Channel modulators

Some paroxysmal movement disorders, including periodic paralysis, episodic ataxia, and alternating hemiplegia, are probably caused by abnormalities in the channels that transport small molecules such as potassium, sodium, or calcium across cell membranes. Therefore, these disorders may respond to medications that affect the behavior of these channels. Such medications include acetazolamide (Diamox), carbamazepine (Tegretol), topiramate (Topamax), and calcium-channel blockers, (e.g., flunarizine [Sibelium], nifedipine [Procardia Adalat], etc.). Common side effects include drowsiness, low blood pressure, and nausea.

Botulinum and Other Toxins

Botulinum toxin is a synthetic form of the toxin produced by the bacterium clostridium botulinum. This toxin, in its natural state, occasionally causes severe food poisoning from improperly canned foods and may cause weakness in infants exposed to honey.

Botulinum toxin has led to a revolution in therapy for many children with movement disorders.

When a small amount of the purified form of the toxin is injected directly into muscle, side effects of generalized weakness and gastrointestinal disturbance are avoided; only the targeted muscle becomes weak.

This has been used as a very successful therapy for improving muscle stiffness in children with spasticity or dystonia. The use of botulinum toxin injections has led to a revolution in therapy for many children with movement disorders. Botulinum toxin is used in combination with physical therapy and, in some cases, along with serial casting. This combination approach helps to loosen muscles for correct positioning. It may also be used to predict the effect of surgery on the muscles.

The effects of botulinum toxin are temporary and full muscle strength usually returns within 3 to 6 months; therefore, if an undesired result occurs, there is no permanent effect. Unfortunately, this also means that to achieve desired results, most children need injections every 3 to 6 months. These injections are moderately uncomfortable and sometimes require sedation or, in some cases, anesthesia.

The exact mechanism of the beneficial effect of botulinum toxin remains under debate. The toxin operates by impairing the ability of nerves to release the transmitter acetylcholine onto muscle; thereby, it weakens the muscle contraction. However, the toxin has this same effect on the intrinsic muscle fibers that are used to sense muscle stretch. Therefore, the possibility has been raised that part of its effect in spasticity is due to a decrease in the signals sent from the muscle stretch receptors back to the spinal cord.

There are two currently available forms of botulinum toxin: botulinum toxin type A (BOTOX, Dysport [in Europe]), and botulinum toxin type B (Myobloc). Both toxins have similar effects. Occasionally, if a child develops immunoresistance to one form of botulinum toxin, the other form may still be effective. The toxin is injected directly into the affected muscles, often at several locations. When more than one muscle is involved, multiple injections are needed. The total dose given to a child cannot exceed certain safety limits. Often it is necessary to use EMG to clarify muscle activity and record these activities as well as to electrically stimulate the muscle to ensure that the toxin injection targets the correct muscle.

There are no known severe side effects of botulinum toxin therapy. Most commonly, when it is first attempted in a child, the dosage is only approximate so that there is either insufficient effect or excessive weakness. It is possible to have pain, bleeding, or infection at the injection site; an allergic reaction is also possible. It is theoretically possible that an injection directly into a vein could cause more diffuse weakness and gastrointestinal problems, but this almost never occurs.

If the initial botulinum toxin injection is helpful, the child returns for further injections when the effects have worn off. This interval must be at least three months. The dosage may need to be adjusted or different muscles targeted in order to maximize the effects. After an injection, the full effect may require 2 to 3 weeks to be seen. Often the physician examines the child 2 weeks after the injection to determine its effects and plan future injections. If the effects are not as desired, they usually wear off completely within 3 to 6 months.

Phenol and alcohol injections have also been used to weaken muscles. Their effects tend to be permanent and the injections are often considerably more painful than those of botulinum toxin. Phenol and alcohol injections have the advantage of not requiring continued treatments. These injections are significantly less expense but the major disadvantage is that of irreversible effects.

Source:  We Move.  Visit their website at www.wemove.org/kidsmove/
Kids Move is WE MOVE's  Web site devoted to pediatric movement disorders. Healthcare professionals and parents  may access up-to-date information about the recognition, assessment, treatment, and avenues of support that are  available for individuals concerned with childhood movement disorders