*Feature : Parkinson's disease'
What Happens in Parkinson's Disease?
In Parkinson's disease, for reasons that are not fully understood, nerve cells in the part of the brain that produces dopamine, the substantia nigra, begin to decrease in number. This causes a decrease in the amount of the available dopamine. Also, the chemical in the synapse that breaks down the dopamine (MAO-B) continues to deplete what little dopamine is left. The overall effect is a large loss of dopamine in the brain. This throws off the normal dopamine/acetylcholine balance.
The result of this imbalance is a lack of coordination of your movement that often appears as tremor, stiff muscles and joints, and/or difficulty in moving. Currently, there is no way to stop the loss of nerve cells that produce dopamine or to restore those that have already been lost. However, there are several methods, including drug therapy, that can help you manage the slow decline in function that occurs with Parkinson's disease.
Normally, we don't even think about how it's possible for our bodies to move -- it just happens when we want it to. But before reading more about Parkinson's disease and its treatment, you will probably find it helpful to understand a little more about how the movement of your body is controlled.
Many different areas within the brain are involved in a complex chain of decisions required for even the smallest muscular movement. For an action like walking, for example, the brain must first gather all the information it needs about your body position. For example, are you sitting, lying down, or already standing up? Where are your feet? Do you have your balance? Then, the brain must add in what it knows about where you will be going. For example, do your eyes tell your brain that you'll be crossing an open field of grass or a busy street? Do your feet detect that the ground is easy to walk on or that you could lose your balance because it is bumpy or slippery?
This information comes together in a central area of the brain, called the striatum, which controls many aspects of bodily motion. The striatum works with other areas of the brain, including a part called the substantia nigra, to send out the commands for balance and coordination. These commands go from the brain to the spinal cord through nerve networks to the muscles that will then help you to move
The entire nervous system is made up of individual units called nerve cells. Nerve cells actually serve as a "communication network" within your body. To communicate with each other, nerve cells use a variety of chemical messengers called neurotransmitters. Neurotransmitters carry messages between nerve cells by crossing the space between cells, called the synapse
Neurotransmitters also allow the nervous system to communicate with the body's muscles and translate thought into motion. One especially important messenger is dopamine, which is manufactured in the substantia nigra. Dopamine is crucial to human movement and is the neurotransmitter that helps transmit messages to the striatum that both initiate and control your movement and balance. These dopamine messages make sure that muscles work smoothly, under precise control, and without unwanted movement.
When a dopamine message is needed, a nerve cell that produces dopamine gathers packets within itself filled with dopamine particles. These packets carrying the dopamine move to the end of the nerve cell, open a "window," and release the dopamine particles into the synapse. The dopamine particles flow across the synapse and fit into special pockets on the outside of the neighboring, or receiving, nerve cell. The receiving cell is now stimulated to send on the message, so it gathers its own packets of dopamine and passes along the message to the next nerve cell in the same way.
After the receiving cell has been stimulated to pass along the message, the pockets then release the dopamine back into the synapse. To fine-tune coordination of movement, these "used" dopamine particles, along with any excess dopamine that did not originally fit into a pocket on the receiving cell, are broken down by a chemical in the synapse called MAO-B. This is an important step in the precise control of muscle movement. Too much or too little dopamine can disrupt the normal balance between the dopamine system and another neurotransmitter system, and interfere with smooth, continuous movement.
The other neurotransmitter system that works in conjunction with the dopamine system to produce smooth movement uses a messenger called acetylcholine. Some of the nerve cells in the brain are specialized to use either dopamine or acetylcholine to send different messages, depending on what it is you want to do.
One way to illustrate how the muscle control process works is as follows: two buckets - one for the dopamine system and one for the acetylcholine system - balanced on either end of a seesaw. This depicts the situation at rest when the dopamine and acetylcholine systems are balanced. When you decide to move, your brain understands the movement you want to make and it sends out a balance of dopamine and acetylcholine messages to keep that movement smooth.
Communication is an essential part of human nature. It is used in a variety of ways: to maintain social ties, give and receive information, gain or hold employment, and share thoughts and feelings. Inability to communicate effectively can result in withdrawal, depression, or hostility directed toward others.
Many people report improved communication and swallow function following speech therapy. Therapy graduates have stated; "I feel like my voice is alive again!", "I have more confidence", "It is easier to swallow my medication now", and other testimonials to the numerous benefits of speech therapy.
Speech, voice tone and inflection, and facial expressions are all important aspects of communication. Consider all the instances in which speech is crucial: talking on the phone, sharing stories with the family, summoning a pet, making financial transactions, scheduling appointments, etc.
Voice tone and inflection project emotions and feelings. The use of voice tone varies with different people: a grandchild, telemarketer, boss, doctor, store clerk - all elicit different inflections.
Facial expressions are also an essential aspect of communication. When first meeting someone, much information is conveyed through facial expression alone: happiness, excitement, fear, or sadness.
Imagine talking with someone whose speech is unclear, whose voice is flat, and whose facial expression appears "blank". What message is conveyed? These features may be interpreted as lack of comprehension or lack of interest in the conversation. However, these same features may be symptomatic of Parkinson's disease.
Facial masking or lack of facial expression is common in PD. This symptom is often described as having a "poker face". This masking is a result of rigidity and reduced movement in the muscles of the face. Some people with PD report feeling like friends, family members and even strangers do not think they are interested in everyday conversations or perceive them as not understanding the conversation due to this lack of expression.
Parkinson disease, a slowly progressive neurological condition, can affect the coordination of muscles used for speech and voice. It is estimated that 75% of individuals with PD experience changes in speech and voice production at some point through the course of the disease. These changes range from mild to severe. but usually fall within the moderate range. Four percent of individuals report changes in speech and voice as the first PD symptom noticed.
Changes within the speech and voice system typically occur over an extended period of time. Often, the individual with PD is unaware of these changes because of the very gradual decline in function. Just as a spouse or friend may be the first to notice reduced arm swing or altered gait, the same may be true for changes in speech and voice.
The same physical symptoms that can occur in the limbs - reduced movement, rigidity, tremors, etc. - can also occur in the speech system. These symptoms are classified as hypokinetic dysarthria. "Dysarthria" simply refers to a speech disorder due to a change in muscle control. "Hypokinetic" means reduced movement. Thus, hypokinetic dysarthria is reduced movement of the muscles used for speech production.
Parkinson dysarthria can affect respiration (breathing), phonation (voice production), resonation (richness of voice), and articulation (clarity of speech). This includes muscles for breathing and muscles within the voice box, throat, soft palate, tongue, lip and jaw. Parkinson's disease, however, primarily affects the coordination and movement of the muscles used for respiration, phonation, and articulation.
If the vocal folds do not close completely, air can escape through them causing a softer, weaker voice and occasionally, a complete loss of voice. A hoarse voice or changes in voice quality are also frequently observed in individuals with PD. Some people wonder if they have developed chronic allergies or post-nasal drip. when actually it may be changes occurring in the vocal folds. Such changes can create a hoarse or raspy voice.
Other vocal or phonatory system characteristics reported in PD are breathiness, vocal tremor or unsteadiness in the voice, and a strained or strangled-sounding voice. These characteristics all result from changes in the control of muscles of the voice box and respiratory system, or from compensatory techniques an individual may be using to counteract changes within the vocal system.
The resonating system determines the richness of the voice, and is judged by whether or not it sounds as if someone is "talking through the nose". Changes within this system may be a result of the soft palate or velum not moving as well as it should.
Normally, the soft palate, located in the back of the roof of the mouth, closes off the nasal cavity while speaking, except when producing nasal sounds such as "m...", "n...", or "ing...". In Parkinson's disease, the soft palate may not move adequately, which allows air to leak into the nose, creating a nasal quality in the voice.
The articulatory system is comprised of the muscles of the face, lips, tongue, and jaw. While speaking, these muscles move at rapid speeds as well as in a coordinated manner. This allows for clear and precise speech. Often individuals with PD notice that their words are not formed or enunciated as clearly as they once were. Some people report "slurred" or mumbled speech. These changes are not usually the result of muscle weakness or paralysis (as in individuals who have suffered a stroke).
Imprecise articulation in PD is attributed to reduced movement and reduced range of motion, tremor, dyskinesias (involuntary movements), or lack of coordination of the face, jaw, lip and /or tongue muscles.
The following is an example of how articulation is affected by reduced movement in the facial muscles: Think about a time when your face was very cold. You might have noticed that it was difficult to move your facial muscles and your speech became slightly slurred or unclear. This sensation is similar to the one experienced by individuals with reduced movement in the facial muscles.
MUMBAI: Even 180 years after it was first described by James Parkinson as `paralysis agitans' or the shaking palsy, Parkinson's disease, as it later came to be known, has defied a cure. While its pathology is better understood today, its cause continues to remain a matter of scientific inquiry. Even its diagnosis has remained purely clinical so far.
Still, at the end of this century, medicine is more capable of easing the suffering of Parkinsonians, even if it is only at the symptomatic level, says Dr Laszlo Tamas, director of Neurological Surgery at the Pacific Neurosciences Institute in Orinda, California.
A clinical associate professor of neurosurgery at Stanford University, Dr Tamas is currently in the city to share information on new advances in the surgical treatment of Parkinson's disease with neurosurgeons at Jaslok Hospital. A superspecialist in stereotactic functional neurosurgery, his primary work at the moment is in the area of deep brain stimulation for patients with advanced Parkinson's disease.
We know the part of the brain which is the site of the damage-- the substantia nigra--in Parkinson's. We now not only understand the chemical involved, dopamine, but also its effects on the different pathways of the brain.
In the 1980s, while investigating a group of drug-abusing patients in California who came down with early Parkinson's, we identified a specific toxin, MPTP, as a causative agent for the disease. Now, a search is on for other such toxins.
The general feeling is that a genetic susceptibility, balanced with environmental stimuli, are responsible for the disease.
One has to differentiate between treatments that address the actual disease--that is, the death of cells in the substantia nigra--and treatments that address the symptoms. There has been tremendous progress on both fronts.
In another decade or two, we will have really powerful therapies to address the actual cell death that goes on. We don't have them now, but there are many researchers making efforts in different directions with regard to fetal tissue transplantation, transplanting pig tissue, or transplanting manufactured cells.
However, while we can't make Parkinson's go away, we have made quite big advances in treating its symptoms, such as tremors and rigidity. And that has been a tough learning curve because, unlike most diseases which are diseases of structure, Parkinson's is more a disease of function. Thus, the primary purpose of treatment is to improve function and allow the person to lead as normal and independent a life as possible.
First we have the drugs, which are most useful in the early stages of the disease. Then, there's destructive surgery, such as Thallamotomy and Pallidotomy that target specific areas of the brain and destroy cells in order to improve body movements. Newer approaches include implanting electrodes to influence and modulate parts of the brain (Deep Brain Stimulation) and treatment to interrupt brain pathways with focused radiation rather than surgery.
All these therapies must be used judiciously. Since Parkinson's is a specific disease connected to a specific part of the brain, so the ideal treatment for it should also be highly specific.
The neurologist follows a patient over many years and tries many different things and then hands over the baton to the neurosurgeon.
It also depends on the particular patient's history--how long h/she has had the disease, whether the problem is more one of tremors or gait disturbance. Surgery strongly benefits tremors and rigidity but not so much slowing of movement or gait disturbance. Also, if the effect of the drugs starts wearing off faster, or side-effects like dyskinesia or uncontrolled movements increase substantially, it may be time to consider surgery.
In DBS, an electrode is implanted in the brain--either in the thalamus region of the brain (most likely place for tremors), or in the Globus Pallidus (very strong effect on Dyskinesia) and now in a new area called the sub-thalmic nuclei-- through a small hole drilled in the skull. A wire runs just under the scalp down to the collarbone, where a pacemaker-sized battery is implanted. It sends electrical waves to the electrode, which emits constant, tiny electrical shocks customised to block whatever you are targeting, such as tremors or rigidity.
Imaging is the first step to locate the target area or the landmarks close to it. The second step is putting the electrode there with one millimetre accuracy, using stereotactic techniques.
You could remove the biggest brain tumour successfully and feel very proud of it, but the patient may not feel a difference immediately. But when you do DBS, you can see a perceptible difference in the operation room--the tremor just stops and it is a magnificent sight.
DBS can also be used to treat the essential tremor in some people with multiple sclerosis, rare patients with head injuries, dystonia, and some of those with cerebral palsy. Stimulation can be made appropriate for a person by manipulating and controlling the strength of the electric current.
There is a parallel fight going on, funded primarily by private industry, to attack the basic cause of the disease. Gene therapy is one arm of the fight--directly injecting genes into certain places to turn on certain enzymes which will lead to the chemical restoration in the brain. I think in our lifetime, we should see a cure for Parkinson's. And in 20 years, there should be decent enough therapies for the actual primary problem. I just don't know which one we should bet on today.
