What Is Parkinsons Disease
Parkinsons disease is a progressive condition that causes trouble with movement. Its caused by the death of cells in a part of the brain called the substantia nigra. This part of your brain produces the neurotransmitter dopamine.
In some cases, specific genetic mutations are linked to the development of Parkinsons. But more often, it seems to appear randomly. Its thought that environmental factors such as exposure to pesticides, herbicides, or air pollution may contribute, but more evidence is needed to understand the potential link.
According to the National Institute on Aging, Parkinsons most commonly develops in people over the age of 60 and affects men about 50 percent more often than women.
Cause Of Essential Tremor
Essential tremor is the most common type of tremor, and affects more people than Parkinsons disease. Some estimates suggest that around 1 in 5 people over the age of 65 years is affected.
There is no known cause, but a genetic link is strongly suspected. Each child of a person with essential tremor has a 50% chance of inheriting the disorder themselves. If a person with essential tremor has other affected family members, then the disorder is called familial tremor.
Causes Of Parkinsons Disease
Parkinsons disease is caused by a loss of nerve cells in part of the brain called the substantia nigra. This leads to a reduction in a chemical called dopamine in the brain.
Dopamine plays a vital role in regulating the movement of the body. A reduction in dopamine is responsible for many of the symptoms of Parkinsons disease.
Exactly what causes the loss of nerve cells is unclear. Most experts think that a combination of genetic and environmental factors is responsible.
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Dopamine Modulates Parkinsons Tremor Through The Vim And Pallidum
The VIM plays a causal role in the generation of Parkinsons tremor, as shown by the ability of VIM deep brain stimulation to reduce tremor . Furthermore, cerebral activity in the entire cerebello-thalamo-cortical-circuit is reduced after VIM-DBS, as shown by FDG-PET . Accordingly, based on functional MRI data, we have previously suggested that the VIM is involved in modulating resting tremor amplitude, analogous to a light dimmer . The current results show that dopamine reduces tremor-related activity in the VIM, possibly by increasing thalamic self-inhibition. In turn, this may disrupt tremor amplification by the VIM, resulting in tremor suppression. This finding fits with previous observations that levodopa specifically reduced thalamo-cortical oscillatory coupling in tremor-dominant Parkinsons disease patients , and that it increased the participation of the thalamus to a sensorimotor network in drug-naïve Parkinsons disease patients .
In addition to the VIM, the pallidum is also one of the key players in the generation of tremor , e.g. GPi-DBS is very effective in reducing tremor . Accordingly, we previously showed that the GPi drives tremulous activity in a cerebello-thalamo-cortical motor loop , and that pallidal dopamine depletion was correlated with resting tremor severity . The current finding that dopamine reduced tremor-related activity in the pallidum provides further support for the idea that pallidal dopamine depletion leads to tremor-related activity.
How To Treat Parkinsons Tremor
Medication is the most effective way of treating Parkinsons tremor. Anticholinergic drugs like benztropine, orphenadrine, and trihexyphenidyl are the most commonly prescribed drugs. These drugs act by blocking the action of acetylcholine, which is a neurotransmitter involved in muscle movement. This action of anticholinergics results in the activity of brain cells responsible for movement. Drugs that are used to treat other symptoms of Parkinsons disease could also help to relieve the tremor.
A surgical approach called deep brain stimulation is used when all the prescribed drugs fail to control the tremor. It involves a surgery during which electrodes are installed inside the brain of a patient. The electrodes produce a current that helps to get rid of the abnormal brain activity that caused the tremor. The current is adjusted with the help of a pacemaker-like device placed in the upper chest area.
Hand exercises like flicking the hand, spinning a pencil, and squeezing a ball may also be useful.
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Relationship Between Univariate And Dynamic Causal Modelling Results
We investigated the effects of dopamine on tremor-related cerebral activity using both univariate and multivariate analyses.
Importantly, both analyses are consistent in that they point towards the VIM as a key target of dopaminergic medication, even though both analyses are fundamentally different. More specifically, the univariate analysis reports the effect of dopamine on the statistical dependency among tremor amplitude and cerebral activity . This type of analysis does not take inter-regional dependencies into account. Thus, dopamine may influence one brain area that in turn produces downstream effects in another brain region . To test whether the effect of dopamine on the VIM was mediated by other nodes in the tremor circuitry, we used DCM. DCM is a multivariate approach that takes into account the tremor-related and spontaneous dynamics of the entire network. Therefore, statistical evidence for a particular model is not dependent on significant effects of dopamine in individual nodes . We compared multiple models in which we varied the site where dopamine was allowed to affect network activity. The model in which dopamine directly influenced the VIM won convincingly from other models in which dopamine influenced the basal ganglia . This suggests that dopaminergic medication influenced the VIM directly, instead of indirectly through the basal ganglia.
How Is Essential Tremor Treated
If you have essential tremor, you might find there are things that make it worse, such as stress, caffeine, alcohol and some medicines such as asthma medicines, Ritalin or lithium. Avoiding these triggers can help.
If needed, your doctor might prescribe medicine to decrease the tremor. Possible medicines include:
- beta blockers propranolol is the most commonly prescribed of the beta blockers, which are widely used to lower blood pressure
- anti-epileptic medicines such as primidone and gabapentin
- muscle relaxants such as alprazolam
Your doctor might suggest surgery if you are among the few people who have severe shaking despite avoiding triggers and taking prescribed medicines. Surgery to treat essential tremor may involve stimulation of an area in the brain called the thalamus and this procedure is known as deep brain stimulation.
If you notice that your hands shake and you dont know why, make sure that you talk to your doctor to get the right diagnosis and treatment.
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Are My Tremors Associated To Parkinsons Disease
Several neurological conditions can cause tremors and having tremors does not necessarily mean you have Parkinsons disease.
Tremors associated to Parkinsons disease are resting tremors, which occur when the body part is inactive. This typically starts in one hand, fingers, or a foot. Tremors can also affect the jaw or tongue, which can lead to communication difficulties.
As with stiffness, Parkinsons tremors mainly affect one side of the body.
If you think you have resting tremors, consult your doctor. They will perform tests to exclude any other condition often confused with Parkinsons disease.
What Treatments Are Available For Tremors
Of all Parkinsons disease symptoms, the effect of drug treatments on tremors are the most unpredictable.When starting Parkinsons medicine treatments, you and your family should not judge their effectiveness by decreased tremors, but the simplification of daily tasks.Some medication, such as anticholinergics and propranolol, can be specifically used to treat tremors. However, they are not recommended for the elderly.When tremors become too overwhelming, deep brain stimulation can be considered. This is the most effective and reliable treatment available for tremors.Some medications can make your tremors worse. Discuss this with your neurologist.
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Clinical History And Testing
Diagnostic tests can be used to establish some features of the condition and distinguish them from symptoms of other conditions. Diagnosis may include taking the persons , a physical exam, assessment of neurological function, testing to rule out conditions that may cause similar symptoms, brain imaging, to assess cognitive function,, or myocardial scintigraphy. Laboratory testing can rule out other conditions that can cause similar symptoms, such as abnormal , , , or vitamin deficiencies that may cause symptoms similar to dementia.
Typical dementia screening tests used are the and the . The pattern of cognitive impairment in DLB is distinct from other dementias, such as AD the MMSE mainly tests for the memory and language impairments more commonly seen in those other dementias and may be less suited for assessing cognition in the Lewy body dementias, where testing of visuospatial and executive function is indicated. The MoCA may be better suited to assessing cognitive function in DLB, and the scale and the may help understand cognitive decline relative to fluctuations in DLB. For tests of attention, , , and can be used for simple screening, and the Revised Digit Symbol Subtest of the may show defects in attention that are characteristic of DLB. The , and are used for evaluation of executive function, and there are many other screening instruments available.
The Tremors Of Parkinsons Disease
The distinction between these different tremors is not always visible to the naked eye. For example, resting tremor can re-emerge during postural holding, making it difficult to clinically distinguish it from essential tremor. This distinction can be made by focusing on the delay between adopting a posture and the emergence of tremor: in essential tremor there is no delay, while Parkinsons disease resting tremor re-emerges after a few seconds . Since the frequency of re-emergent and resting tremor can be similar, it has been hypothesized that both tremors share a similar pathophysiological mechanism. One interesting patient with Parkinsons disease had no resting tremor, but a marked 36Hz postural tremor that occurred after a delay of 24s following postural holding , thus resembling re-emergent tremor. Such observations point to heterogeneity in the circumstances under which the classical Parkinsons disease resting tremor occurs.
In the following sections, we will mainly focus on the classic resting tremor in Parkinsons disease. We will first describe the clinical and cerebral differences between patients with tremor-dominant and non-tremor Parkinsons disease. Then we will detail how these differences may inform us about the causes and consequences of Parkinsons disease resting tremor.
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Summary Of The Modeling Results
The modeling shows that anatomical and membrane properties of subthalamo-pallidal circuits are prone to generation of tremor-like bursting in the presence of relatively strong basal ganglia-thalamo-cortical feedback. As we strengthen synaptic projections in the network , the tremor-like oscillations become more prominent. The destruction of the feedback leads to the suppression of the tremor-like oscillations .
The dependence of the strength of tremor-like oscillations on the strength of dopamine-dependent synaptic projections is not monotonic. Based on the simple model setup, one can hardly specify which range of synaptic parameters corresponds to the actual range of variation of the synaptic strength experienced in Parkinsons disease. Moreover, the effects of adding in dopamine agonist are not necessarily opposite to the effects of dopamine depletion taking place in Parkinsons disease. However, the model study demonstrates the general pattern of the change: as the basal ganglia-thalamo-cortical feedback loop becomes stronger, oscillations are likely to occur. The phenomenon is robust with respect to different kinds of modulation of the dopamine-dependent parameters. The phenomenon is also robust with respect to different values of delays in the feedback loop. While the actual delays are not likely to change in Parkinsons disease, they are not well-known. But the studied phenomenon persists for different values of delays.
What Treatments Are Available
Treatment depends on the symptoms and extent of disability caused by the tremor. If the tremor is mild, lifestyle adjustments may be all that are needed. As the condition progresses, medications or surgery can be used to relieve the symptoms.
Lifestyle changes
Caffeine and stress should be avoided, and good sleep is recommended. Your doctor may recommend physical therapy, which can improve your muscle strength. Adaptive devices, including wide-grip pens and eating utensils, may help you compensate for your tremor. Alcohol, used in moderation, can reduce tremor for short periods of time.
Medications
Your doctor may prescribe certain drugs or injections to help reduce the tremors. These include, but are not limited to:
- Propranolol, a beta-blocker that is primarily used to treat high blood pressure
- Anti-seizure medications, including primidone, gabapentin, and topiramate
- Anti-anxiety medications, including clonazepam, diazepam, lorazepam, and alprazolam
- Botulinum toxin injections for head and voice tremors
Surgical treatments
The goal of surgery is to reduce symptoms by modifying the abnormal signals that cause the tremor. This can be done with deep brain stimulation or with radiosurgery.
DBS surgery involves implanting electrodes within the brain and connecting them to a stimulator device that resembles a pacemaker. The stimulator delivers electrical pulses to regulate brain activity. Radiosurgery creates a small, permanent lesion in the brain without a permanent implant.
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The Effect Of Dopaminergic Modulation
To study the effects of dopaminergic modulation we varied dopaminergic parameters s1 and s2 as proxy for the presence of dopaminergic modulation . The results of the previous subsection suggest that the strength of the feedback is essential for the occurrence of bursting, so we varied the dopaminergic parameters in a broad range to see how bursty the discharge is .
As an example, we consider the SNR1 as we vary the dopaminergic parameter s1 in the interval , . As the dopaminergic parameter increases, SNR1, which indicates the presence of the tremor-related bursting , decreases, first moderately, then sharply to less than 1 . Thus, Figure 3 illustrates the transition between tremulous and non-tremulous case, as the dopaminergic action changes. Of note is a relatively sharp onset of tremor oscillations in the model and jagged profile of SNR. We think this is most likely due to the simplicity of the model. While gross structure is captured by the model, the exact details of oscillatory/nonoscillatory transition in the model depend on a particular set of bifurcations the model experiences as the parameters are varied. This bifurcation cascade is likely to be model-specific. Moreover, if dopamine-dependent parameters are varied in different ways, the SNR profile may be different.
What Is A Resting Tremor
A Parkinsons tremor differs from most other types of tremor because it is a resting tremor. It happens most often when a body part is relaxed rather than in motion. For a Parkinsons patient, a hand may quiver when resting in a lap or when holding a utensil to the mouth while eating.
Most tremors are “action tremors” where the shaking happens when a person moves their muscles. These may occur when holding arms outstretched, holding a heavy item in one position, or reaching slowly and purposefully toward an object.
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Parkinsons Tremors Vs Essential Tremors
Because they can be similar to Parkinsons tremors, essential tremors are often confused as symptoms of the disease. Just as with Parkinsons, essential tremor can cause uncontrollable rhythmic shaking in different parts of the body.
Up to 10 million people are affected by this common nervous system disorder. While genetics and environment likely play a role in essential tremor, the cause is unknown, according to the U.S. National Library of Medicine.
Essential tremors in the hands or arms can be distinct from Parkinsons because they typically happen when the hands are in use.
The essential tremor can get really bad when youre using your limb when drinking or eating soup, for example, says Gilbert. The Parkinsons tremor is usually not as disabling whereas the essential tremor can be life-altering.
The shaking from an essential tremor typically improves when using both hands to bring a cup to the mouth but the same action can amplify the tremor in Parkinson’s, according to Gilbert.
Dr. Beck points out that an essential tremor may be faster than a Parkinsons tremor, which tends to be milder. A difference can often be seen in a persons handwriting. Those with essential tremor tend to have more unsteady and wavy writing, whereas Parkinsons patients are more apt to display micrographia, or abnormally small handwriting.
They have low amplitude movement so their writing gets smaller and smaller to a point where it can be barely legible, he says.
What Are The Symptoms Of Parkinsons Disease
The main symptoms of Parkinsons disease are:
- tremor or shaking, often when resting or tired. It usually begins in one arm or hand
- muscle rigidity or stiffness, which can limit movement and may be painful
- slowing of movement, which may lead to periods of freezing and small shuffling steps
- stooped posture and balance problems
The symptoms of Parkinsons disease vary from person to person as well as over time. Some people also experience:
- loss of unconscious movements, such as blinking and smiling
- difficulties with handwriting
- drop in blood pressure leading to dizziness
- difficulty swallowing
- sweating
Many of the symptoms of Parkinsons disease could be caused by other conditions. For example, stooped posture could be caused by osteoporosis. But if you are worried by your symptoms, it is a good idea to see your doctor.
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How Can I Reduce Tremors
In the early stages of Parkinsons disease, some people can reduce tremors by pressing or rolling a ball, pen or other small object. Tremors can also increase during stressful situations, during which you should take some time to breath and relax.
Tremors are more difficult to control during the more advanced stages of the disease. Here are some ways to better manage your tremors if they interfere with daily activities:
- Write on a keyboard rather than by hand
- Use speech-to-text cell phone apps
- Drink with a straw
- Use heavier utensils. If this does not help, you can purchase electronic utensils designed to counter your tremors
- Purchase clothing and shoes that are easy to put on
More Than Just Dopamine
While it may seem that the whole problem of tremors in PD is completely caused by deficient dopamine production in the substantia nigra, that is not the case. There are several reasons that we know there is more to a resting tremor than just a dopamine deficiency.
- The most effective treatment for symptoms of PD are medications that increase dopamine or prolong the action of dopamine in the brain. Even when dopamine is adequately replaced, a person with advanced PD may still experience tremors.
- The regions of the brain that are involved in PD, including the thalamus, globus pallidus, cerebral cortex, and the cerebellum, often show structural and metabolic deficits in PD, suggesting that deficits in these structures are involved in causing the condition.
- Surgical treatment that is effective for PD symptoms is targeted toward a number of regions in the brain, including the globus pallidus and subthalamic nucleus.
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