Cognitive And Psychological Differences In Patients With Essential Tremor
Benign essential tremor is probably the most common of all movement disorders. Someone with essential tremor has increased shakiness, usually of the hands or arms, whenever the limb is being used.?? This distinguishes the tremor from that of classical Parkinson’s disease, which is usually worse when the arm and hand are at rest.
Tremors In Parkinsons Disease: What They Are Types Of Tremors And More
Getting the trembling associated with Parkinson’s under control can be a challenge, but treatments can help.
Don RaufJustin Laube, MDNicole Rerk/Shutterstock
Tremors are a defining characteristic of Parkinson’s disease, affecting about 8 out of 10 people with this movement disorder. Many people think the involuntary shaking motion is the main problem for patients. While it is certainly an irritating symptom that individuals want to get under control, other characteristics of the disease can be more debilitating.
What Does Benign And Essential Mean In Benign Essential Tremor
The term “essential” is not meant to indicate the tremor’s value. The shaking is an annoyance and can even be debilitating in some cases. The word “essential” is intended to indicate that tremor is the only symptom involved — that it’s the “essence” of the entire problem. Similarly, the word “benign” signifies that the disorder, while annoying, is not inherently dangerous.
These views, while comforting and widely held, might be wrong.
For one thing, essential tremor is probably not actually just one disease, but rather a symptom caused by any one of a number of different processes.?? Some of these may indeed be “benign,” but others may be more serious.
What Lifestyle Changes Can I Make To Ease Parkinsons Symptoms
Exercise: Exercise helps improve muscle strength, balance, coordination, flexibility, and tremor. It is also strongly believed to improve memory, thinking and reduce the risk of falls and decrease anxiety and depression. One study in persons with Parkinson’s disease showed that 2.5 hours of exercise per week resulted in improved ability to move and a slower decline in quality of life compared to those who didn’t exercise or didn’t start until later in the course of their disease. Some exercises to consider include strengthening or resistance training, stretching exercises or aerobics . All types of exercise are helpful.
Eat a healthy, balanced diet: This is not only good for your general health but can ease some of the non-movement related symptoms of Parkinson’s, such as constipation. Eating foods high in fiber in particular can relieve constipation. The Mediterranean diet is one example of a healthy diet.
Preventing falls and maintaining balance: Falls are a frequent complication of Parkinson’s. While you can do many things to reduce your risk of falling, the two most important are: 1) to work with your doctor to ensure that your treatments — whether medicines or deep brain stimulation — are optimal; and 2) to consult with a physical therapist who can assess your walking and balance. The physical therapist is the expert when it comes to recommending assistive devices or exercise to improve safety and preventing falls.
Improve the quality of your sleep.
What Is A Tremor And What Makes It Different With Parkinsons
Tremor is an uncontrollable, rhythmic muscle contraction that triggers quivering in one or more parts of the body. It often occurs in hands, arms, or legs but can also affect the head, neck, or torso. This shaking may appear in sporadic spells or continue constantly.
The National Institute of Neurological Disorders and Stroke says that age is a risk factor — middle-aged and older adults are more likely to experience tremors.
Tremor And Loss Of Physical Control In Parkinson’s Disease
Often, the first symptoms of Parkinson’s disease to appear are in the upper limbs. People had discovered there were things that they had always done without a second thought, like opening a door or combing their hair, that for some reason they now have difficulty doing or may not be able to do at all. What they can’t understand is why they can no longer do them. As Natalia described it, “To move papers around, the message doesn’t get to my hands and my brain doesn’t give the message what to do.” Khadim said it felt as though someone was pulling at his hand stopping him from moving it.
What Are The Surgical Treatments For Parkinsons Disease
Most patients with Parkinson’s disease can maintain a good quality of life with medications. However, as the disease worsens, medications may no longer be effective in some patients. In these patients, the effectiveness of medications becomes unpredictable – reducing symptoms during “on” periods and no longer controlling symptoms during “off” periods, which usually occur when the medication is wearing off and just before the next dose is to be taken. Sometimes these variations can be managed with changes in medications. However, sometimes they can’t. Based on the type and severity of your symptoms, the failure of adjustments in your medications, the decline in your quality of life and your overall health, your doctor may discuss some of the available surgical options.
What Is The Outlook For Persons With Parkinsons Disease
Although there is no cure or absolute evidence of ways to prevent Parkinson’s disease, scientists are working hard to learn more about the disease and find innovative ways to better manage it, prevent it from progressing and ultimately curing it.
Currently, you and your healthcare team’s efforts are focused on medical management of your symptoms along with general health and lifestyle improvement recommendations . By identifying individual symptoms and adjusting the course of action based on changes in symptoms, most people with Parkinson’s disease can live fulfilling lives.
The future is hopeful. Some of the research underway includes:
- Using stem cells to produce new neurons, which would produce dopamine.
- Producing a dopamine-producing enzyme that is delivered to a gene in the brain that controls movement.
- Using a naturally occurring human protein – glial cell-line derived neurotrophic factor, GDNF – to protect dopamine-releasing nerve cells.
Many other investigations are underway too. Much has been learned, much progress has been made and additional discoveries are likely to come.
What Medications Are Used To Treat Parkinsons Disease
Medications are the main treatment method for patients with Parkinson’s disease. Your doctor will work closely with you to develop a treatment plan best suited for you based on the severity of your disease at the time of diagnosis, side effects of the drug class and success or failure of symptom control of the medications you try.
Medications combat Parkinson’s disease by:
- Helping nerve cells in the brain make dopamine.
- Mimicking the effects of dopamine in the brain.
- Blocking an enzyme that breaks down dopamine in the brain.
- Reducing some specific symptoms of Parkinson’s disease.
Levodopa: Levodopa is a main treatment for the slowness of movement, tremor, and stiffness symptoms of Parkinson’s disease. Nerve cells use levodopa to make dopamine, which replenishes the low amount found in the brain of persons with Parkinson’s disease. Levodopa is usually taken with carbidopa to allow more levodopa to reach the brain and to prevent or reduce the nausea and vomiting, low blood pressure and other side effects of levodopa. Sinemet® is available in an immediate release formula and a long-acting, controlled release formula. Rytary® is a newer version of levodopa/carbidopa that is a longer-acting capsule. The newest addition is Inbrija®, which is inhaled levodopa. It is used by people already taking regular carbidopa/levodopa for when they have off episodes .
What Does This Mean For Me If I Have Essential Tremor
There is compelling evidence that cognition differs between people with and without an essential tremor. Those differences, however, are slight, and the cause of those changes is unclear. If essential tremor is, in fact, a degenerative illness, it’s very slow.?? How this all relates, if at all, to patient care is unclear at this time. Perhaps identifying more serious causes of essential tremor could end up benefiting people who would otherwise be written off as having an entirely benign disorder.
DISCLAIMER: The information in this site is for educational purposes only. It should not be used as a substitute for personal care by a licensed physician. Please see your doctor for diagnosis and treatment of any concerning symptoms or medical condition.
What Are The Different Categories Or Types Of Tremor
Tremor is most commonly classified by its appearance and cause or origin. There are more than 20 types of tremor. Some of the most common forms of tremor include:
Essential tremor
Essential tremor is one of the most common movement disorders. The exact cause of essential tremor is unknown. For some people this tremor is mild and remains stable for many years. The tremor usually appears on both sides of the body, but is often noticed more in the dominant hand because it is an action tremor.
The key feature of essential tremor is a tremor in both hands and arms, which is present during action and when standing still. Additional symptoms may include head tremor without abnormal posturing of the head and a shaking or quivering sound to the voice if the tremor affects the voice box. The action tremor in both hands in essential tremor can lead to problems with writing, drawing, drinking from a cup, or using tools or a computer.
Tremor frequency may decrease as the person ages, but the severity may increase, affecting the person’s ability to perform certain tasks or activities of daily living. Heightened emotion, stress, fever, physical exhaustion, or low blood sugar may trigger tremor and/or increase its severity. Though the tremor can start at any age, it most often appears for the first time during adolescence or in middle age . Small amounts of alcohol may help decrease essential tremor, but the mechanism behind this is unknown.
Dystonic tremor
Cerebellar tremor
What Are The Different Stages Of Parkinsons Disease
Each person with Parkinson’s disease experiences symptoms in in their own unique way. Not everyone experiences all symptoms of Parkinson’s disease. You may not experience symptoms in the same order as others. Some people may have mild symptoms; others may have intense symptoms. How quickly symptoms worsen also varies from individual to individual and is difficult to impossible to predict at the outset.
In general, the disease progresses from early stage to mid-stage to mid-late-stage to advanced stage. This is what typically occurs during each of these stages:
Early stage
Early symptoms of Parkinson’s disease are usually mild and typically occur slowly and do not interfere with daily activities. Sometimes early symptoms are not easy to detect or you may think early symptoms are simply normal signs of aging. You may have fatigue or a general sense of uneasiness. You may feel a slight tremor or have difficulty standing.
Often, a family member or friend notices some of the subtle signs before you do. They may notice things like body stiffness or lack of normal movement slow or small handwriting, lack of expression in your face, or difficulty getting out of a chair.
Mid stage
Mid-late stage
Standing and walking are becoming more difficult and may require assistance with a walker. You may need full time help to continue to live at home.
Advanced stage
Cognitive And Emotional Aspects Of Essential Tremor
A growing number of scientists have described subtle differences in how people with essential tremor perform on neuropsychological tests.?? In one study, people with essential tremor performed worse than the control group on tests of memory, attention, and concentration.
In addition to these cognitive differences, people with essential tremor have been described as being at an increased risk for depression, as well as to suffer from anxiety or social phobias.?? Some studies have described patients with essential tremor as more introverted, rigid, or lonely than the general population. All of these characteristics, though, were described by comparing groups of people, meaning that there is still a lot of variation between individuals.
Causes Of Resting Tremors In Parkinson’s Disease
Resting tremors are among the most noticeable features of Parkinson’s disease .?? The tremors are believed to be caused by complex interactions between a number of factors. Alterations in the activity of several areas of the brain including the substantia nigra, the basal ganglia, and the thalamus, as well as changes in the level and action of the neurotransmitter dopamine, are all related to each other and to the production of the tremors.
Tremors Not Associated With Parkinsons Disease
There are different types of tremors, of which not all are associated with Parkinson’s disease, and they vary slightly in terms of how, when and where they manifest in the body. They include essential tremor and dystonic tremor and may be associated with other conditions and genetic mutations, although a specific gene has not been identified.
A patient with a Parkinson’s tremor typically will find that their symptoms worsen and spread to other parts of the body over time. Generally, the tremor starts in one hand and can progress to the arm and foot on the same side of the body, and then eventually to the other side of the body. In severe cases, tremors also can affect the jaw or lips.
The Role Of The Cerebellum In Essential Tremor
Certainly, many studies have suggested that the cerebellum does not function normally in essential tremor. This may explain why some people with essential tremor have other “cerebellar findings” on their neurological examination, such as ataxia or poor hand-eye coordination.??
In the last decade, we have become increasingly aware that the cerebellum does more than coordinate movement — it may help to coordinate thoughts and perhaps emotions as well. Studies have connected cerebellar activity with the dorsolateral prefrontal cortex, a region of the brain classically associated with problem-solving, attention, and memory.??
Which Body Parts Do Parkinsons Tremors Affect
There are five main places you’ll have Parkinson’s tremors:
1. Hands. Parkinson’s disease tremors often start in the fingers or hands with what’s called a pill-rolling motion. Imagine holding a pill between your thumb and index finger and rolling it back and forth.
2. Foot. A Parkinson’s foot tremor is more likely to happen while you’re sitting or lying down with your feet at rest. If the tremor moves into your thigh muscles. It could look like your whole leg is shaking.
Foot tremors disappear when you stand or walk because those are active movements. A foot or leg tremor while you’re standing may be another condition.
3. Jaw. This is common in people with Parkinson’s. It may look like you’re shivering. It can become bothersome if the tremor makes your teeth chatter. If you wear dentures, it could make them shift or fall out.
Chewing eases the tremor, so gum might help.
4. Tongue. It’s rare, but a tongue tremor can cause your entire head to shake.
5. Internal. Some people with Parkinson’s say they can feel a shaking sensation in their chest or abdomen. But can’t be seen from the outside.
What Are The Symptoms Of Parkinson’s Disease
Symptoms of Parkinson’s disease differ from person to person. They also change as the disease progresses. Symptoms that one person gets in the early stages of the disease, another person may not get until later—or not at all.
Symptoms most often start between the ages of 50 and 60. They develop slowly. They often go unnoticed by family, friends, and even the person who has them.
The disease causes motor symptoms and non-motor symptoms. Motor symptoms are those that have to do with how you move. The most common one is tremor.
Tremor and other motor symptoms
Tremor, or shaking, often in a hand, arm, or leg, occurs when you’re awake and sitting or standing still . It gets better when you move that body part.
- Tremor is often the first symptom that people with Parkinson’s disease or their family members notice.
- At first the tremor may appear in just one arm or leg or only on one side of the body. The tremor also may affect the chin, lips, and tongue.
- As the disease progresses, the tremor may spread to both sides of the body. But in some cases the tremor stays on just one side.
Emotional and physical stress tends to make the tremor more noticeable. Sleep, complete relaxation, and intentional movement or action usually reduce or stop the tremor.
The most common cause of non-Parkinson’s tremor is essential tremor. It’s a treatable condition that is often wrongly diagnosed as Parkinson’s.
Besides tremor, the most common symptoms include:
What Are The Symptoms Of Parkinsons Disease
Symptoms of Parkinson’s disease and the rate of decline vary widely from person to person. The most common symptoms include:
Other symptoms include:
- Decreased facial expressions: You may not smile or blink as often as the disease worsens; your face lacks expression.
- Speech/vocal changes: Speech may be quick, become slurred or be soft in tone. You may hesitate before speaking. The pitch of your voice may become unchanged .
- Handwriting changes: You handwriting may become smaller and more difficult to read.
- Depression and anxiety.
- Sleeping disturbances including disrupted sleep, acting out your dreams, and restless leg syndrome.
- Pain, lack of interest , fatigue, change in weight, vision changes.
- Low blood pressure.
How Do I Prevent Falls From Common Hazards
- Floors: Remove all loose wires, cords, and throw rugs. Minimize clutter. Make sure rugs are anchored and smooth. Keep furniture in its usual place.
- Bathroom: Install grab bars and non-skid tape in the tub or shower. Use non-skid bath mats on the floor or install wall-to-wall carpeting.
- Lighting: Make sure halls, stairways, and entrances are well-lit. Install a night light in your bathroom or hallway and staircase. Turn lights on if you get up in the middle of the night. Make sure lamps or light switches are within reach of the bed if you have to get up during the night.
- Kitchen: Install non-skid rubber mats near the sink and stove. Clean spills immediately.
- Stairs: Make sure treads, rails, and rugs are secure. Install a rail on both sides of the stairs. If stairs are a threat, it might be helpful to arrange most of your activities on the lower level to reduce the number of times you must climb the stairs.
- Entrances and doorways: Install metal handles on the walls adjacent to the doorknobs of all doors to make it more secure as you travel through the doorway.
Essential Tremor Is Not Parkinsons Disease
Essential tremor and Parkinson’s disease are different conditions. Essential tremor is characterised by shaking when movement starts, which can continue or worsen during movement. The symptoms of Parkinson’s disease include:
- involuntary tremor when you are not moving
- muscle stiffness
- slowness of movement
- ‘freezing’.
Parkinson’s disease is caused by a lack of supply of the brain chemical dopamine, which is necessary for smooth and controlled muscular movement.
Consider Tremor Along With Other Symptoms
“Parkinson’s reputation is that it is a tremor disease, and that’s how you can identify it across a crowded room,” says Rebecca Gilbert, MD, PhD, chief scientific officer for the American Parkinson Disease Association in New York City.
Although tremors bring people to diagnosis in many cases, defining the condition as a tremor disease may have done patients a disservice over the years because there are more severe symptoms that people struggle with. Tremor is just the one that people can see, according to Dr. Gilbert.
“Many think if you don’t have a tremor everything is fine,” she says. “That isn’t true.”
Over time, other disease features, such as cognitive problems, psychosis, blood pressure irregularities, depression, and lack of desire to do things, can be more devastating.
James Beck, PhD, chief scientific officer with the Parkinson’s Foundation, also cautions that tremor may not be the first distinguishing feature.
“A person may notice a slowness of movement called bradykinesia,” he says. “Or someone may be walking down the street and one arm doesn’t swing. These symptoms may appear before tremor.”
While focusing only on tremor may not be advisable, understanding this abnormal movement and treatment options may help patients improve their quality of life.
What Are The Symptoms Of Essential Tremor
If you have essential tremor, you will have shaking and trembling at different times and in different situations, but some characteristics are common to all. Here is what you might typically experience:
- Tremors occur when you move and are less noticeable when you rest.
- Certain medicines, caffeine or stress can make your tremors worse.
- Tremors may improve with ingestion of a small amount of alcohol .
- Tremors get worse as you age.
- Tremors don’t affect both sides of your body in the same way.
Here are signs of essential tremor:
- Tremors that are most obvious in your hands
- Difficulty doing tasks with your hands, such as writing or using tools
- Shaking or quivering sound in your voice
- Uncontrollable head-nodding
- In rare instances, tremors in your legs or feet
Parkinsons Tremors Vs Essential Tremors
Because they can be similar to Parkinson’s tremors, essential tremors are often confused as symptoms of the disease. Just as with Parkinson’s, 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 Parkinson’s because they typically happen when the hands are in use.
“The essential tremor can get really bad when you’re using your limb — when drinking or eating soup, for example,” says Gilbert. “The Parkinson’s 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 Parkinson’s tremor, which tends to be milder. A difference can often be seen in a person’s handwriting. Those with essential tremor tend to have more unsteady and wavy writing, whereas Parkinson’s 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.
When To Be Concerned About Hand Tremors
Someone with a severe tremor can have their hands shaking uncontrollably. Fact is, everybody has the potential to experience tremors in some form. Dr. Tom Miller talks with movement disorder specialist Dr. Lauren Schrock about the two main types of tremors and how to identify the differences between them, possible causes, and when to be concerned.
May 20, 2014
Parkinsons Disease Can Be Misdiagnosed
In the early stages, it can be difficult to diagnose Parkinson’s disease. The early symptoms of the disease can come and go. You might think you are just stiff or having cramps. Or, you might think that this is just part of the aging process. But if the symptoms keep on coming back, you will eventually go to the doctor. He may tell you that it may take more time before he can make a definite diagnosis. This can lead to much anxiety, of course.
If you think you might have Parkinson’s disease, below are some things to keep in mind, especially if your doctor has not yet diagnosed you. Remember, diagnosing PD can be hard, even for a highly trained neurologist:
- There are no blood tests or lab tests that can diagnose the disease for certain. It is usually diagnosed based upon medical history, a clinical exam and symptoms.
- Four typical signs of PD are rigidity, slow movement, tremors and postural instability. If you are experiencing these symptoms, especially if they began on one side of the body, your doctor may diagnose you with the disorder.
Note that even if you have three classic symptoms of PD, you still may not have it! To decrease the chance that you will be misdiagnosed, your doctor may have you take several drugs that treat Parkinson’s such as levodopa. If your symptoms get better when you take the drug, you probably have PD. If you do not get better after a period of levodopa therapy, your tremors may be due to another cause.
PD and Progressive Supranuclear Palsy
What Treatments Are There For Tremors
Parkinson’s tremors cannot be cured. However, there are several options to manage them.
Many of the typical Parkinson’s drug treatments are associated with a reduction in tremors, including levodopa and dopamine agonists. A surgical procedure called deep brain stimulation also may be offered to control unmanageable tremors.
Physical therapy can help some patients control their tremors better, as can reducing the intake of substances such as caffeine, which can induce tremors. Many patients experience an increase in the severity of their tremors when they are stressed. Therefore, trying to reduce sources of anxiety and engaging in complementary therapies may help some patients.
Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Diseases That Mimic Essential Tremor
To be diagnosed with essential tremor, one must first exclude known mimics.?? More serious problems such as multiple sclerosis, traumatic brain injury, tumors, vascular disease, Wilson’s disease, atypical Parkinson’s disease, drugs, toxins, and more can cause a tremor that worsens when the hand and arm are in use. If one of these things is found to be the cause of the tremor, the tremor is not considered “essential,” but part of a more serious medical condition.
The controversy begins after we have excluded as many of those disorders as possible, and only the tremor seems to remain. Even then, there may be hints that the tremor is a sign of a wider, more involved process in the body.
What Looks Like Parkinsons But Isnt
Dr. Fernandez describes two main Parkinson’s mimics:
Essential tremor. Also known as benign essential tremor or familial tremor, this movement disorder causes brief, uncontrollable shaking.
It most often affects your hands, but can also affect your head and neck, larynx and other areas. In rare cases, it affects your lower body as well.
But one clue can help distinguish essential tremor from Parkinson’s.
“This is not an absolute rule, but if shaking occurs at rest, it often is Parkinson’s. And if shaking occurs in action, such as when you’re writing or eating, it is essential tremor,” Dr. Fernandez says.
About half of those with essential tremor have a family history of the condition.
Unlike Parkinson’s, essential tremor is generally not perceived as a progressive disorder, and, if mild, may not require treatment.
Doctors can prescribe medications to reduce shaking, but they are not the same drugs used to treat Parkinson’s, he says.
Drug-induced Parkinson’s. Along with shaking, this condition may cause many symptoms similar to Parkinson’s disease, including stiffness, slow movement, a decrease in facial expression and a change in speech.
As the name suggests, taking certain drugs, most commonly antipsychotics and mood stabilizers, can trigger this condition. How long it takes to develop can vary greatly, depending on which drug you’re taking, how long you take it and the dosage.
How Is Parkinsons Disease Diagnosed
Diagnosing Parkinson’s disease is sometimes difficult, since early symptoms can mimic other disorders and there are no specific blood or other laboratory tests to diagnose the disease. Imaging tests, such as CT or MRI scans, may be used to rule out other disorders that cause similar symptoms.
To diagnose Parkinson’s disease, you will be asked about your medical history and family history of neurologic disorders as well as your current symptoms, medications and possible exposure to toxins. Your doctor will look for signs of tremor and muscle rigidity, watch you walk, check your posture and coordination and look for slowness of movement.
If you think you may have Parkinson’s disease, you should probably see a neurologist, preferably a movement disorders-trained neurologist. The treatment decisions made early in the illness can affect the long-term success of the treatment.
Can Parkinsons Disease Be Prevented
Unfortunately, no. Parkinson’s disease is long-term disease that worsens over time. Although there is no way to prevent or cure the disease , medications may significantly relieve your symptoms. In some patients – especially those with later-stage disease, surgery to improve symptoms may be an option.
How Are Parkinsons Tremors Treated
Tremor can be unpredictable. Some experts say it’s the toughest symptom to treat with medication. Your doctor may prescribe medication for your tremors:
- Levodopa/carbidopa combination medicines . This treatment is a type of medication called a dopamine agonist. It’s usually the first treatment for Parkinson’s.
What Are The Treatments For Tremor
There is no cure for most forms of tremor, but there are treatments to help manage symptoms. In some cases, the symptoms may be so mild that you do not need treatment.
Finding the right treatment depends on getting the right diagnosis of the cause. Tremor caused by another medical condition may get better or go away when you treat that condition. If your tremor is caused by a certain medicine, stopping that medicine usually makes the tremor go away.
Treatments for tremor where the cause is not found include
- Medicines. There are different medicines for the specific types of tremor. Another option is Botox injections, which can treat several different types.
- Surgery may be used for severe cases that do not get better with medicines. The most common type is deep brain stimulation .
- Physical, speech-language, and occupational therapy, which may help to control tremor and deal with the daily challenges caused by the tremor
If you find that caffeine and other stimulants trigger your tremors, it may be helpful to cut them from your diet.
NIH: National Institute of Neurological Disorders and Stroke