Where Is It At?
The Dystonia Foundation holds regular medical conferences where dystonia
experts from all over the world discuss advances in research. It is encouraging
to see that this work has now given rise to increased interest in dystonia
among researchers. Earlier this year, for example, the U.S. government
announced a new program to support scientists who wish to study "the causes
and mechanisms of dystonia."
At a symposium held in Atlanta this summer, it was reported that "dramatic
progress" is being made in dystonia research. Here are some of the advances
made in recent years.
Thanks to genetic research, in 1995 it was discovered that a rare form
of dystonia called dopa-responsive could be practically cured with a drug
called levodopa. It was discovered that with this form of dystonia a gene
deficiency leads to a lowered production of a chemical called dopamine
that plays a crucial role as a message transmitter in the brain. The problem
can be corrected by raising the level of dopamine with small doses of levodopa.
The two children that appeared on Oprah Winfrey's "It's A Miracle" earlier
this month have dopa-responsibe dystonia. It is the only form of dystonia
that benefits from medication so remarkably. When the discovery was made,
doctors began giving levodopa to patients with other forms of dystonia,
but without success.
Recently scientists have traced the defective gene in a form of generalized
dystonia to abnormalities in a gene they have called DYT1. Only about 30%
of carriers of the gene develop symptoms. If a person carries the gene
but still has no symptoms by the age of 28, he or she may live the rest
of their lives without symptoms.
The DYT1 gene is the code for a protein called TorsinA whose exact function
is still unknown. Scientists speculate that it is also associated with
an imbalance in dopamine signalling in the brain. Whatever it does, it
is clear that it interferes with the developmental process of the brain.
Researchers are looking into this.
Here in Ottawa Dr. David Grimes is researching another form of inherited
dystonia called inherited myoclonus-dystonia (IMD). Dr. Grimes explains:
"It is a rare form of dystonia that normally begins in childhood. Individuals
affected often have both dystonia and another involuntary movement called
myoclonus. Myoclonus is a rapid jerking movement that can affect any muscle
in the body. The basic understanding of this form of dystonia is just beginning
to be unravelled as two different genes have now been implicated in its
cause. The first gene is called the D2 dopamine receptor gene found on
chromosome 11. However it is not clear at this point whether this gene
can cause the disease on it's own or not. The second gene called epsilon
sarcoglycan is found on chromosome 7 and is involved in supporting the
cells' outer covering. It seems at this point that in many individuals
with IMD, their dystonia is caused by abnormalities in this gene."
This discovery has prompted a whole new thinking on how this particular
form of dystonia could be caused, says Dr. Grimes. Recently IMD has also
been linked in one family to a area on chromosome 18. A specific gene defect
has not been found yet but other cell covering genes that are found in
this area on chromosome 18 are currently being investigated for abnormalities.
"Understanding how rare sub types of dystonia are caused will improve our
understanding of the more common forms of dystonia," says Dr. Grimes.
Problems with Sensory Process
Many people with dystonia know from experience that sometimes they can
prevent an abnormal movement by moving in a particular way, by lifting
their arms, touching their face, singing out loud, holding a straw protruding
from their mouth, etc. These are called "sensory tricks" (geste antagoniste)
and scientists have been investigating this phenomenon. They discovered
that there is a sensory deficit in dystonia and the "sensory tricks" may
be an instinctive attempt to correct it.
Dystonic movements are characterized by simultaneous contraction of
muscles that move the body in opposite directions. In properly executing
a movement the muscle to be activated must be excited while the opposite
muscle and other nearby muscles must be inhibited. Research now believes
that there is a loss of inhibition in dystonia. The pathway to the central
brain that is responsible for exciting the muscles is working fine but
the pathway responsible for inhibiting the opposite muscles is not. The
"sensory tricks" might play the role of causing the required inhibition.
Researchers are presently investigating this using different approaches
like drugs or "brain retraining" exercises.
The introduction of botulinum toxin in the late 1980's revolutionized
the treatment of dystonia. Botox has become the most used therapeutic tool
in the treatment of blepharospasm, oromandibular dystonia, spasmodic dysphonia,
cervical dystonia, and writers cramp and other limb dystonias. But it does
not work for everyone.
Various drugs are used to treat dystonia with relative success, but
there is no consistency and often patients choose to do without the side
effects. Scientists recognize that the treatment of dystonia with drugs
is largely based on empirical rather than scientific rationale. In other
words, if a particular drug works for you, keep using it, but there is
no explanation for why it works. Drugs called "anticholinergics" have been
found to be most useful in the treatment of generalized and segmental dystonia.
Other drugs that are sometimes useful are the benzodiazepines, baclofen,
and anticonvulsants such as carbamazepine. Of course you may know them
as Ativan, Clonazepam, Lorazepam, etc.
The real progress in terms of drugs is that patients, talking with their
doctors, learn as they go about dosage and when to take it.
Most importantly, it has become clear that patient education, physical
therapy, complementary therapies, healthy living and supportive care are
very important integral elements of a comprehensive treatment of dystonia.