Ms hand tremors: MS Tremors (Postural, Intention, Nystagmus) Causes & Treatment
MS Tremors (Postural, Intention, Nystagmus) Causes & Treatment
What Is a Tremor?
A tremor is when a body part moves or shakes and you can’t control it. Many people with multiple sclerosis (MS) have some form of tremor they can’t control, in different parts of their bodies, like their head, arms, or legs.
What Are the Types of Tremors?
- Intention tremor. There’s no shaking when you’re at rest. It starts when you try to reach or grasp something or move your hand or foot to a precise spot. This is the most common form of MS tremor, and it usually causes the most problems in day-to-day life.
- Postural tremors. You shake when you sit or stand, but not when you lie down.
- Resting tremor. You move more when you’re sitting still and less when you move. This is more common with Parkinson’s disease than MS.
- Nystagmus. This type causes jumpy eye movements.
Why Does MS Cause Tremors?
This disease damages the protective sheath (myelin) that covers the nerves in your brain and spinal cord. Tremors result from damage to a part of your brain called the cerebellum. It controls your balance and coordination and smooths out the actions that you make when you move your limbs and eyes or speak.
Medicines That Treat MS Tremors
These problems are one of the hardest MS symptoms to treat. There aren’t any drugs made just to treat MS tremors. Your doctors will probably prescribe drugs for another condition, like:
Nonmedicinal Tremor Treatments
- Braces: These can hold your joint still and stop extra movement. A brace on your ankle or foot can make it easier to walk. They can help control your arm, hand, or neck, too.
- Deep brain stimulation: This experimental approach is mostly used for people who have tremors from Parkinson’s disease. A doctor implants electrodes into your brain. Wires connect them to a gadget in your chest. You use it to send your brain signals that stop the tremors.
- Medical cannabis: There’s little evidence that cannabis can help with tremors, but study results are mixed and usually only include small numbers of people.
- Physical therapy: It can show you exercises that increase your range of motion, improve your posture and balance, and make your body more stable
- Speech therapy: If you have tremors in your lips, tongue, or jaw, a health professional can work with you to slow your speech, make it clearer, and control the volume.
- Occupational therapist: This person will set you up with special tools called adaptive or assistive devices. They can help you grab things from up high or off the floor, pull up a zipper, or hold a fork more easily.
- Weights: Adding extra weight to a body part can help keep it still. You can also add weights to commonly used items like forks, pencils, pens, eating utensils, canes, and walkers.
Tremors and Depression
Tremors can be tough to handle in social situations. You may feel like you want to be alone, but that can make you feel lonely and depressed. A psychologist or counselor can help you find ways to feel more comfortable in public and keep the tremors from changing how you live your life.
Tremor as a Symptom of Multiple Sclerosis
Tremor—shaking that you can’t control—is a common symptom of multiple sclerosis (MS) that usually develops after at least five years of having the disease, though this isn’t a hard-and-fast rule. Tremors can occur when you’re trying to do something with your hands, whether you’re standing or sitting, and their severity can range from being barely noticeable to significantly interfering with your daily tasks.
Verywell / JR Bee
Signs and Symptoms
Tremors are involuntary muscular contractions that result in a rhythmic, back-and-forth movement of a specific body part. While your hands are most often affected, tremor also can affect your legs, vocal cords, head, and trunk. It can come and go or get progressively worse with time.
There are a number of different kinds of tremors, but the two main types in MS include:
- Intention tremor: This is the kind of tremor that occurs when you reach for something and your hand starts shaking. The closer you get to your target or the smaller the movement required, the more your hand or arm will shake. This is the most common type of tremor in MS.
- Postural tremor: This is a shaking that occurs while you’re sitting or standing and your muscles are trying to hold parts of your body still against the force of gravity. Another example is shakiness when you hold your arms out in front of you.
If you have a tremor in your jaw, lip, or tongue, this may affect your ability to swallow (dysphagia) or to speak clearly (dysarthria).
For the majority of people, tremor is mostly annoying, may make everyday tasks more difficult, and can be embarrassing. However, a small percentage of people may experience tremor so severe that it becomes impossible to perform necessary tasks like eating, drinking, or getting dressed.
It’s important to note that you shouldn’t experience either intention tremor or postural tremor when you’re asleep or even just lying down and your muscles are relaxed. If you have a tremor while you’re resting, this may be the result of something else, since resting tremors are rare in MS, so be sure to talk to your doctor about it.
Like other MS symptoms, most MS tremors are caused by demyelination—damage by the body’s immune system to myelin, the protective sheath around your nerves. In the case of tremors, the demyelination takes place in your cerebellum or the nerves leading to or away from it. The cerebellum is the part of your brain that controls balance and coordination, and it helps to make the movements of your limbs, mouth, and eyes smooth and fluid.
Tremor can also be the result of demyelination in the thalamus, the part of your brain that controls the motor systems in your body, and the basal ganglia, which are located on either side of the thalamus in your brain and help control movement.
Tremor can occur as a relapse symptom and disappear on its own or after a course of corticosteroids, though it’s also common for a residual tremor to remain.
The severity of tremor is not linked to how long you’ve had MS.
Around 45 percent to 47 percent of MS patients experience tremors, with 5.5 percent to 5.9 percent reporting severe tremor, according to a 2015 study.
Because there are no official treatment guidelines for MS-related tremor, it can be a tricky symptom to treat. It’s often a trial-and-error process to see which approaches work best for you, and as your symptoms change, you may need to explore different treatment options.
Keep in mind that even though treatment can reduce your tremors, it most likely won’t eliminate them completely.
There aren’t any specific medications for treating tremors, so doctors usually prescribe the following drugs off-label, which means they’re not approved by the U.S. Food and Drug Administration (FDA) for treating MS-related tremor.
Medications your doctor may prescribe include:
- Benzodiazepines: e. g., Klonopin (clonazepam)
- Anticonvulsant: e.g., Neurontin (gabapentin), Mysoline (primidone), or Keppra (levetiracetam)
- Antihistamines: e.g., Atarax or Vistaril (hydroxyzine)
- Beta blockers: e.g., Inderal (propranolol)
- Antispasmodics: e.g., baclofen or Zanaflex (tizanidine)
- Antiemetics: e.g., Zofran (ondansetron)
- An antibiotic called Nydrazid (isoniazid)
A 2016 study of 567 participants with MS tremors found that 47 percent used medication to treat them. The majority of those using medication said they had moderate (54 percent) or severe (51 percent) tremor, while the others characterized their tremors as mild (37 percent) or completely disabling (35 percent).
In the patients who reported moderate or severe tremor, only around half said that medication helped reduce their tremors. Anticonvulsants were the most often used class of medications (51 percent), followed closely by benzodiazepines (46 percent). Though most participants only used one medication, some used two or three medications for relief.
A 2018 review of studies on treatments for upper-limb tremors in patients with MS showed that Nydrazid (isoniazid) has been the most-studied pharmacologic intervention to treat tremor and helped relieve it in 60 percent to 80 percent of patients. However, the studies were all quite small and conducted in the 1980s.
The review also noted that a 2014 study of the effect of disease-modifying therapies on tremor established that patients taking Tysabri (natalizumab) were more likely to report improvement in their tremor than those on other forms of disease-modifying drugs.
Additionally, the researchers found that the most commonly noted side effects across the board for all the medication options for tremor were fatigue and weakness.
For many MS patients, a rehabilitative plan that involves one or more forms of therapy can reduce tremor.
An occupational therapist can help you find and learn to use special equipment that assists you with daily activities, such as braces for affected joints, weights for affected areas or for items you need to use, and other aids for writing, cooking, eating, and getting dressed.
Occupational therapy can also help you learn strategies for coping with tremor and maintaining good posture and alignment when you’re carrying out your activities of living.
If your tremors affect your balance, coordination, and ability to walk, you may especially benefit from physical therapy. A physical therapist can give you exercises that strengthen your core, improve your balance, and keep you active and flexible, as well as help you develop good posture and alignment, all of which can reduce your tremor.
In cases of tremors that affect your jaw, lips, and/or tongue, speech therapy may be helpful. A speech therapist can teach you how to speak more slowly and clearly by adjusting the placement of your jaw, tongue, and lips. He or she can also advise you on communication aids if you need them.
If your tremor is severe and other treatment options haven’t worked for you, surgery may be an option. There are two types of surgeries that can be used to treat MS tremors.
Deep Brain Stimulation (DBS)
This method, also known as thalamic stimulation, has been the surgery of choice for MS-related tremors for the last couple of decades. In DBS, the surgeon places battery-operated electrodes in your thalamus that deliver small electric currents to stimulate certain areas, lessening your tremors.
In stereotactic thalamotomy, also known as lesion surgery, a specific area in your thalamus is destroyed using radiofrequency or focused ultrasound. These precise locations are located before the surgery on a magnetic resonance imaging (MRI) scan or a computerized tomography (CT) scan. Essentially, this destruction prevents your brain from transmitting signals that cause your tremors.
Thalamotomy is permanent and can cause side effects like weakness, fatigue, and seizures, though these may go away with time.
A 2019 review of studies on DBS and thalamotomy in patients with tremor, some of which included MS-related tremor, concluded that both types of surgery are equally effective in successfully reducing tremor and improving quality of life. The researchers also did a subgroup analysis that indicated that thalamotomy that’s performed with focused ultrasound may improve quality of life even more than other types of thalamotomy or DBS.
Only two small studies, one from 1997 and another from 2012, have been done so far on the effects of botulinum toxin injections on MS tremor.
The 2012 study utilized electromyography (EMG) guidance to inject the 23 participants with either Botox (onabotulinumtoxinA) or placebo in targeted areas of one or both arms where their tremors appeared. After 12 weeks, the participants received the reverse treatment.
The researchers found that Botox significantly improved hand tremors and coordination difficulties, called ataxia, which in turn decreased the amount of disability the tremors caused. And though around 42 percent of the participants developed mild to moderate weakness after the Botox injection, this went away completely within two weeks.
Botulinum toxin injections may be an option to decrease your tremors, especially if you can’t take medications, you aren’t experiencing enough relief with other treatments, or you’re not a candidate for surgery. Talk to your doctor about whether or not this is a viable choice for you.
You can take practical steps to keep yourself healthy, which can help you cope with your tremors and other MS symptoms more effectively. Consider trying the following.
- Minimize stress: Delegate tasks to others whenever possible, make time for yourself, and learn relaxation techniques like aromatherapy and deep breathing, which can help you deal with stressful situations.
- Choose a healthy diet: A diet that’s rich in vegetables, fruits, and whole grains gives you the nutrition you need to stay healthy.
- Exercise as much as you’re able: Moving around is good for your muscles and your waistline, and it can help with MS symptoms.
- Eliminate or reduce caffeine and tremor-inducing medications: If you’re on medications that make your tremor worse (think stimulants or certain asthma medications), talk to your doctor about finding other options. And if caffeine gives you the jitters, work on reducing your intake and potentially eliminating it from your routine altogether.
- See a counselor: Depression and anxiety are common in any chronic illness, and MS is no exception. And since mental health affects your physical health, seeing a therapist when you’re having difficulties can greatly improve not only your mental state, but your overall quality of life too.
A Word From Verywell
Tremor can be one of the more challenging symptoms in MS, and, like every one of them, how tremor affects you is very personal. If you find yourself dealing with it, try to be patient and keep communication open as you and your doctor figure out what treatment options work best. Take each day one at a time and be good to yourself by carving out space for activities you enjoy and keeping yourself healthy. Your body and your mind will both thank you.
Tremor | MS Trust
There are no drug therapies that can completely cure tremor. Those that are available have limited effect, and may have unpleasant side effects, including dependency. The most common drugs prescribed for tremor are beta-blockers, such as propanolol, anti-convulsants such as gabapentin, and benzodiazepams such as clonazepam, which slow down the nerve messages in the body.
Cannabis-based drugs have been investigated in the treatment of tremor, but there is poor evidence to support an effect. Natalizumab improves tremor in some people with MS who take it as a disease modifying drug.
Botulinum toxin (botox) has been used with some success to treat intrusive head or face tremor in people with MS. Botox is a toxin that temporarily paralyses a muscle that is otherwise not under control. It eventually wears off, and repeat injections are needed to maintain the effect.
If your tremor is severe and disabling, and has not responded to drug treatment, then surgery could be an option. The aim of surgery for tremor is to cut off nerve links to the affected area of your brain, or remove it altogether. Thalamotomy is the destruction of part or all of the thalamus. Opening up the skull to perform a thalamotomy has mostly been replaced with deep brain stimulation or surgery using non-invasive methods that do not break the skin. Research shows them to be just as effective as surgery, and to have better safety and recovery results.
Deep brain stimulation (DBS) or thalamic stimulation, which has been used successfully in treatment of Parkinson’s Disease, may also offer an alternative approach to treating tremor in MS. A thin wire is surgically implanted into the brain with a battery-operated pulse generator implanted near the collarbone. The pulse generator sends continuous electrical pulses to the brain, which blocks nerve signals from this area. It has a similar effect to surgical removal of the thalamus, but is reversible if the electrical pulses are stopped. There is a risk of bleeding in the brain with DBS.
Non-invasive surgical procedures sound a bit like they belong on Star Trek, but are now found more often in mainstream medical practice. Stereotactic radiosurgery (SRS), also known as ‘gamma knife’ surgery, uses focused radioactive waves to deliver a very accurate dose of radiotherapy to the brain area that needs to be destroyed.
A similar approach is MR guided focused ultrasound (MRgFUS). This takes place in an MRI imaging suite rather than an operating suite, and is well established as a treatment for fibroids or prostate cancer. UK trials on using this method for tremor began in 2017. The high powered focused ultrasound raises the temperature in an accurately targeted brain region, heating up and killing the selected cells while sparing the surrounding brain tissue.
Although surgery or similar non-invasive procedures often have a beneficial effect on tremor, the effect is quite variable in MS. In many cases, surgery and non-surgical procedures relieve tremor, but only for a few months before it recurs. It is not clear whether these procedures will affect MS progression, and it can be hard to evaluate how successful they were.
Your neurologist or surgical consultant will be able to advise you on whether you are a suitable candidate for surgery, and what the likely outcome will be for you.
Multiple Sclerosis Tremors
Tremor is an involuntary, rhythmic contraction and relaxation of two opposing muscle groups producing oscillatory movements of regular frequency in one or more parts of the body. It is one of the chief features of Multiple Sclerosis (MS), as part of Charcot’s triad of diagnostic symptoms, along with nystagmus and scanning speech.
In MS, tremor affects the upper limbs, and this can impair the quality of life by hindering coordinated or fine motor movements. Thus the presence of tremor is associated with a higher risk of disability or dependent living in patients with MS. Other sites of tremor in MS include the head and neck, the vocal cords, the trunk and limbs.
Type of Tremor
Patients with MS show either a postural tremor or an intention tremor, both of which are large in amplitude. While the first occurs in a body part which is being maintained against gravity, the latter occurs during a movement which is directed towards a target. In this case the amplitude of the tremor increases as the part is moved towards the target with the eyes open.
Types of Tremors in MS – National MS SocietyPlay
Mechanism of Tremor
Cerebellar pathology underlies the tremor in MS, often in a multifocal manner. Cooling the affected arms leads to a dramatic reduction in the intensity of intention tremor. Cooling may lead to reduced muscle spindle function, as the nerve conduction velocity is lowered. As a result, less data enters the cerebellar neuronal loops which produce tremor, relieving the symptoms.
The intention tremor of MS is probably due to altered muscle contractions in response to sensory proprioceptive information from the muscle spindles, tendons, and receptors in the joints and the skin. Proprioception refers to data regarding the velocity and amplitude of a muscular movement which is transmitted via the spinocerebellar pathway.
Assessment of Tremor
There are several methods in use to evaluate the severity of tremor and its impact on the quality of life of the patient. For example, Bain et al developed a 10-point severity-of-tremor scale, while accelerometry and polarized light goniometry are other neurophysiologic tests. Many of these are not designed to measure the ataxia that is associated with tremor in MS, however.
Various drugs have been employed to treat the tremor of MS, often without documented benefit. These include:
- topiramate which inhibits muscular pathways via gaba neuronal transmission
Side Effects of Drugs
These may include the following:
- swallowing difficulties
- liver impairment
- increased muscular weakness
The two techniques used most often to treat MS include:
This refers to selective destruction of a small area of the thalamus, most commonly the nucleus ventralis intermedius (VIM), to inhibit tremor production. Most patients show dramatic improvement immediately after the surgical procedure, which is maintained for more than a year afterwards.
Gamma-knife thalamotomy has been introduced as an alternative to surgical destruction. Unilateral thalamotomy is carried out to prevent an unduly high incidence of side effects.
Deep Brain Stimulation (DBS)
This refers to the placement of an electrode into the brain to suppress tremor production. It produces approximately as good results with respect to tremor reduction as thalamotomy, but the adverse effects appear to be lower in frequency.
Side Effects of Surgical Treatment
These include the following:
- wound infections
- greater risk of hemiparesis
- mental alterations
- bleeding into the brain, such as intracerebral haemorrhage and subdural haematoma
- relapse of MS
Alternate Modes of Treatment
Other treatment avenues include:
- pulsed electromagnetic fields
- physiotherapy, especially of the rehabilitative model using pressure splints
- limb cooling which results in improvement of tremor for up to 45 minutes, and may therefore be useful before undertaking specific manual tasks which involve fine motor activity
- weights worn in the form of a wrist cuff can reduce tremor amplitude
- orthotic appliances aided by computer software can provide functional improvement
- occupational therapy in the form of specialized software to compensate for tremor while using a computer mouse
- restricting the use of substances such as caffeine which increase nervous excitability
- using relaxation techniques
Hand Tremors: Symptoms, Causes & Treatments
Hand tremors, also known as shaky hands, can interrupt your daily life. Hand tremors can vary in their magnitude, frequency, and progression over time. Your tremor might make specialized movements like threading a needle difficult. This condition can also be severe and impact many other aspects of life. In some cases, it can even decrease your quality of life. Below, we will dive into the possible causes of hand tremors, the symptoms, and what treatments may be effective.
Hand Tremors: What Are They?
Symptoms of Hand Tremors
Causes of Hand Tremors
Hand Tremor Treatment
FAQs: Hand Tremors
Hand Tremors: What Are They?
Hand tremors, or shaky hands, may not be life-threatening on their own, but they can still disrupt your life. In some cases, hand tremor may be a signal of neurological issues or degenerative disease. It’s a good idea to seek out your healthcare provider if you’ve suddenly developed or noticed hand tremor.
Although learning more about your health and body on your own is important, an official diagnosis and treatment plan made in conjunction with your doctor is the best course of action to treat hand tremor symptoms.
Symptoms of Hand Tremors
Hand tremors can happen on and off or be constant. Some tremors may occur on their own without associated health problems, but other kinds of tremor may suggest a specific health issue like liver failure or MS.
Symptoms of hand tremor can include the following:
- Involuntary, rhythmic shaking in the hands and arms
- Difficulty writing or drawing
- Issues holding or controlling utensils or cups
- Trembling in one or both hands
- Shaking may worsen with movement
- Tremors may progress over time
Causes of Hand Tremors
Below are some of the underlying causes of tremor outlined by the National Institute of Neurological Disorders and Stroke and temporary conditions that may result in shaky hands.
Although many people associate tremor with Parkinson’s Disease, essential tremor is eight times more common. Essential tremor or ET causes involuntary, rhythmic shaking that is characterized by action tremor with or without intentional movement. It can affect almost any part of your body. This condition most frequently occurs in the hands and it’s especially noticeable during tasks like tying your shoelaces or using a utensil.
Although it’s not life-threatening by itself, it can make daily tasks more difficult and inconvenient, depending on the severity. ET can begin at any age but most commonly affects those over the age of 40. Although there isn’t a cure for essential tremor, there are treatments that may help reduce the frequency and magnitude of tremors under the guidance of your healthcare provider.
Shaking from Parkinson’s Disease is caused when brain cells controlling movement are damaged. Shaking may start with one hand and spread to the other as the disease progresses. You might also move slowly, have a stooped posture, experience balance issues, or deal with stiffness.
Parkinson’s disease is associated with numerous problems such as poor balance, difficulty swallowing, and stooped posture.Tremors from Parkinson’s occur mostly at rest (resting tremor). In most cases, it disappears during movement but comes back when the limb is resting. Forty six to ninety three percent of patients with Parkinson’s disease also experience postural tremors, a type of action tremor that occurs while maintaining a stance. Tremor is the only symptom of Parkinson’s that might get better on its own and usually reaches a plateau in severity.
Multiple Sclerosis (MS)
Multiple Sclerosis (MS) is a degenerative disease that damages a special coating on your nerves called myelin. A common symptom of MS is hand tremor or shaking in other parts of your body. 25% to 58% of MS patients experience tremor.
Most MS tremors are mild but up to a quarter of MS tremor cases are severe. Tremor is typically associated with ataxia or nervous system degeneration. Besides tremor, ataxia can cause stumbling, coordination issues, and speech problems.
For alcoholics, shaky hands can occur when you quit and begin experiencing withdrawal symptoms. Shaky hands can also occur during excessive alcohol use.
Hand tremors and trembling in other parts of the body can begin after only 10 hours after your last alcoholic drink and last for a few weeks. Detox programs sometimes offer addicts medications to help manage hand tremors and other symptoms of withdrawal.
When your liver can’t remove toxins from the blood, you might experience a loss of brain and nervous system function, which is known as hepatic encephalopathy (HE). As a result of HE, tremors, muscle stiffness, confusion, impaired consciousness, and personality changes might occur.
Low Blood Sugar
When your nerves and muscles are low on blood sugar or hypoglycemic, your hands may shake. Since your body relies on blood sugar as its main source of energy, hypoglycemia can disrupt your brain’s ability to function properly. It also causes the release of hormones like epinephrine and norepinephrine, which in turn can cause hand tremor, sweating, increased heart rate, hunger, and anxiety.
Medications and Drugs
Prescription drugs and other substances can cause hand tremors which may include the following:
- Excess thyroid medication
- Epinephrine and norepinephrine
- High blood pressure drugs
- Mood stabilizers
- Asthma medication
- Seizure medication
- Cancer treatments
Poisoning and Toxins
Certain exposure to neurotoxins like heavy metals such as lead, mercury, and arsenic can lead to nerve damage and tremor in the limbs. Research is still ongoing to investigate the potentially harmful impact of exposure to environmental toxins, for example, substances and compounds found in industrial waste.
Stroke and Pre-Stroke
A stroke can cause damage to the cerebellum or basal ganglia in the brain, resulting in a tremor. Shaking and trembling can also be a warning sign of a future potential stroke.
Hand Tremor Treatment
The type of treatment necessary for your tremor depends on the cause. If your doctor determines that your hand tremors are the result of essential tremor, there is no cure. However, there are a variety of pharmaceutical medications and non-pharmaceutical medication treatments available to ameliorate the worst of the symptoms or reduce the magnitude of tremors.
- Beta-Blockers: Beta-blockers, primarily propranolol, are often the first line of defense doctors use to treat the symptoms of essential tremor. Unfortunately, they can result in unpleasant side effects and patients may develop a tolerance to them after a short time period.
- Benzodiazepines: An example is clonazepam (Klonopin), which is a prescription drug. They may reduce the amplitude of tremors, but have a risk of addiction and side effects like drowsiness.
- Anticonvulsants: Anticonvulsants have had medium success in scientific studies and are used as a second line of drugs, sometimes in conjunction with beta-blockers.
- Botox Injections: Botox can help improve hand and voice tremors, but also may weaken muscles resulting in decreased strength in the hand muscles and difficulty swallowing.
Deep brain stimulation (DBS) is used in cases of severe, drug-resistant essential tremor or patients who can’t tolerate the side effects of ET medication. During this surgical procedure, wires tipped with electrodes are implanted in areas of the brain responsible for tremors. These wires funnel through the neck and connect to a neurostimulator in the chest near the collarbone. This neurostimulator generates and sends electrical signals through the wires to the implanted electrodes to help control the symptoms of essential tremor.
Like other surgeries, DBS presents a risk of side effects. Potential side effects include speech issues, worsening of motor symptoms, depression, and falls.
During a focused ultrasound, beams of ultrasound (sound waves) are targeted on an area of the brain’s thalamus, which controls motor and sensory signals. The ultrasound waves heat up and burn the targeted part of the brain and destroy the affected tissue. The burn or lesion created by the ultrasound may be able to interrupt the abnormal tremor movements.
Gamma Knife Radiosurgery
Gamma Knife radiosurgery involves sending targeted radiation in the form of a laser beam to the brain’s thalamus, where it destroys tissue responsible for tremor symptoms. However, neurological side effects are possible, like facial sensory loss and other neurological issues. In addition, improvements in tremor as a result of the procedure may fade over time.
Behavior and Lifestyle Changes
Essential tremor can be affected by emotional stress, nicotine, and caffeine. Limiting stimulants and keeping your stress level down by practicing self-care and prioritizing your mental health can help reduce symptoms of ET.
Here are some other lifestyle changes you can make at home according to Hopkinsmedicine.org:
- Use heavier, sturdier utensils with larger handles for easier gripping
- Invest in clothing with Velcro or button hooks
- Use straws for drinking
- Consider wearing slip-on shoes
- Complete more difficult tasks when your tremors are less noticeable (this might be in the morning, evening, or afternoon)
Cala Trio offers a specialized wristband that helps reduce hand tremors in patients with essential tremor. The wristband works by sending electrical stimulation to your brain and disrupting the network responsible for tremor. This non-invasive therapy is customized for your unique tremor pattern and can help reduce the magnitude of your tremors.
You’ll need to talk to your doctor to find out if this revolutionary treatment is right for you. It can be used alone or alongside your essential tremor medications. It’s important to note that it’s not appropriate to use this medical device if you’ve undergone Deep Brain Stimulation surgery because it can interfere with the embedded neurostimulator. Click here for a complete list of safety information.
FAQs: Hand Tremors
If you still have questions about hand tremors, read through the section below to get answers to common queries.
Can hand tremors get worse?
ET symptoms typically worsen over time at a gradual pace. Most only experience mild to moderate symptoms, while others might suffer from more severe effects. As ET worsens, the tremor frequency might decrease but the intensity of tremors may increase. With treatment, these symptoms can be managed.
What’s the difference between Parkinson’s and essential tremor?
According to Harvard.edu, one of the main differences between the Parkison’s tremor is that the shaking is most noticeable at rest. In contrast, essential tremor is usually most noticeable during movement. Both are dysfunctions of signaling in the brain.
Parkinson’s Disease is associated with other health issues and symptoms like a stooped posture and issues with balance. Essential tremor can get worse over time, impacting the quality of life. . Parkinson’s impacts the quality of life and often limits life expectancy. Who can get essential tremor?
Anyone can get essential tremor, although you’re more likely to get it if you have a family history of the condition. ET can also occur at any age, but onset occurs most often in middle age.
What is Essential Tremor? – Neuravive
What is Essential Tremor?
Essential tremor (ET) is a brain condition that is thought to arise from abnormal electrical brain activity. This leads to uncontrollable shaky movements (tremors) of the hands, limbs, head or voice. It is the most common movement disorder. It can resemble tremors that are symptoms of other conditions, but in fact it is not connected with any other disease. While it usually starts as mild shakiness, often on one side of the body, it is a permanent condition that can worsen over time. Essential tremor is more pronounced during intentional movement such as performing tasks with the hands, and less noticeable when at rest. It is not life-threatening, but if the tremors become severe, ET lessens a person’s quality of life. Daily activity such as drinking from a glass or cup, shaving, writing or typing, buttoning clothes or tying shoelaces can become difficult–even impossible. For those whose jobs depend on hand coordination, it can interfere with their ability to work.
Essential Tremor FAQs
+ Who gets Essential Tremor?
Anyone can develop ET at any age. However, ET is rare in very young children. Most cases develop in adulthood, and the incidence increases with age. Persons with a family history of ET make up about 50% of patients, but specific genetic mutations have not yet been identified. When there is no family history, it is uncertain what causes the abnormal brain activity.
+ Can ET increase the risk of other illnesses
No, having ET does not cause other illnesses. Some symptoms of ET also appear in conditions like Parkinson’s disease, multiple sclerosis, brain injury, etc. but ET is a separate condition. Although ET can worsen over time, it is not a life-threatening disease.
+ How is ET diagnosed?
People with suspected ET should consult with a movement disorder specialist. Because there are no medical tests (e.g. bloodwork) or brain scans that define ET, the doctor will examine the person, and ask about the history of the tremor. A diagnosis of ET is based on answers to questions as well as physical cues that distinguish ET from other conditions that cause tremors.
+ Can ET be cured?
Unfortunately, there is no cure yet for Essential Tremor. Treatment is aimed at reducing tremor severity and improving quality of life. People with mild tremors may initially opt out of treatment until their condition markedly reduces their quality of life. When ET patients do not want medication, or medication no longer works, new treatment approaches like MR-guided Focused Ultrasound (MRgFUS) offer potential long-term symptom relief.
For more information, download the Patient Handbook from the International Essential Tremor Foundation
MRgFUS Neuravive by Sperling Neurosurgery Associates
Neuravive MRI-guided focused ultrasound (MRgFUS) is a new, noninvasive way to control Essential Tremor by correcting it at its source in the brain. It is used when medication no longer works, or a patient does not wish to use medication. Focused ultrasound treatment for essential tremor was approved by the U.S. Food and Drug Administration (FDA) in July, 2016.
Sperling Neurosurgery Associates offers the state-of-the-are Neuravive MRgFUS treatment.
Learn more about Neuravive MRI-Guided Focused Ultrasound (MRgFUS) >>
Neuravive by Sperling Neurosurgery Associates
Neuravive MRI-guided Focused Ultrasound is a breakthrough, non-invasive treatment that reduces or eliminates the symptoms of ET. It is based on MR-Guided Focused Ultrasound (MRgFUS) that utilizes high intensity focused ultrasound guided by Magnetic Resonance Imaging (MRI).
Ultrasound is a form of energy that can pass harmlessly through tissue. It does not involve surgery or radiation. Thanks to brain mapping done by our powerful magnet and specialized software, Neuravive focuses 1,024 beams of ultrasound energy all pinpointed on the very small brain area that is responsible for the tremor, gradually destroying the targeted area. Since the Neuravive procedure is done inside the MRI “bore” (tunnel), high resolution imaging monitors the treatment. When it is over, the result can be an immediate and significant reduction in tremors.
During the procedure, the patient is awake. There are no incisions or holes drilled into the skull, and there is no insertion of electrodes or probes into the brain. Instead, ultrasound waves pass through the brain until they meet at a very small point in the brain (VIM of the thalamus). When the waves intersect at the VIM, they create a tiny ablation or burn. This interrupts the tremor signals. The whole procedure is conducted inside the MRI scanner, enabling the physician to plan, guide, and target the area easily. It also enables precise measurement of the temperature in order to verify that only the intended tissue is targeted and destroyed.
Neuravive is FDA approved. It has been clinically tested, and found to lessen or eliminate Essential Tremor for a minimum of 12 months for nearly 80% of patients. The same study found that MRgFUS produced the fewest side effects at 1 year after treatment when compared with Deep Brain Stimulation (DBS) and radiofrequency thalamotomy.
Only a doctor can evaluate and qualify an ET patient for treatment using the Neuravive MRgFUS.
Find out how we can help you!
If you or someone you love suffers from essential tremor and you’d like to know more about how we can help, call Sperling Neurosurgery Associates today at (908) 956-5946.
Essential tremor, Shaky hands | Mayfield Brain & Spine Cincinnati
Essential tremor (ET) is a disorder of the brain that causes a rhythmic trembling of the hands, arms, head, voice, legs, or trunk. It is not related to Parkinson’s disease. Treatments focus on reducing symptoms and maximizing quality of life. Treatments for this progressive disorder include medication, physical therapy, deep brain stimulation, and radiosurgery.
What is essential tremor?
Essential tremor is an uncontrollable shaking, which usually starts on one side of the body. Tremors occur during purposeful movement, such as when drinking, eating or writing. Many people find the shaking troublesome or embarrassing (Fig. 1). Also known as familial tremor, benign essential tremor, or hereditary tremor, this disorder affects some 10 million Americans. It is a progressive condition that gets worse over time. ET can be treated with medication or surgery, but not cured.
Figure 1. In essential tremor, an area of the brain called the thalamus sends faulty electrical signals causing the hands, arms, head or voice to shake uncontrollably.
What are the symptoms?
Symptoms of essential tremor vary from person to person, as does the rate of progression.
- Rhythmic tremors of the hands, legs, or trunk
- Head nodding in a “no-no” or “yes-yes” motion
- Voice quivering
- Tremors that occur involuntarily and cannot be stopped.
- Tremors that get worse during periods of stress and that lessen during rest.
- In rare cases, mild gait disturbance.
Who is affected?
Essential tremor is more common after age 40 but can affect people of any age, including children. Essential tremor has a genetic component, a variant of the LINGO1 gene. The gene increases the risk of ET, but not everyone with the gene gets ET, and not everyone with ET has this particular genetic variant. Children of a parent with the essential tremor gene have a 50 percent chance of inheriting the gene.
What are the causes?
Scientists do not know the cause of essential tremor. The abnormal electrical brain activity is believed to occur between the thalamus and cerebellum connections. There is no way to prevent ET.
How is a diagnosis made?
There is no medical test that can confirm a diagnosis of ET. Your physician will review your medical history and family history, and will conduct a physical exam. He or she will explore whether another condition is causing your tremors by conducting a neurological exam and ordering laboratory tests. Your doctor also may give you a “performance test,” in which you are asked to drink from a glass, hold your arms outstretched, write your name, or draw a spiral.
Essential tremor is sometimes misdiagnosed as Parkinson’s disease. But whereas people with Parkinson’s often have balance problems, slowness of movement, and freezing of gait, people with ET only rarely have problems in their legs.
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.
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.
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
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 (DBS) 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.
Deep brain stimulation
In DBS surgery, an electrode is placed in a specific area of the brain (usually the thalamus). The electrode is placed on either the left or right side of the brain through a small hole made at the top of the skull. The electrode is connected by a long extension wire that is passed under the skin and down the neck to a battery-powered stimulator under the skin of the chest (Fig. 2). When turned on, the device sends electrical pulses to block the faulty nerve signals that cause tremors.
Figure 2. In essential tremor, the thalamus is suspected of sending faulty messages, causing the shaking hands. A deep brain stimulator electrode can be placed inside the structure to regulate activity. The electrode is connected with a wire to a neurostimulator implanted under the skin of the chest. DBS is similar to a heart pacemaker.
DBS surgery is performed in two stages. Stage 1 is implantation of the electrodes in the brain. About one week later, Stage 2 is performed. This includes implantation of the stimulator device in the chest and tunneling of the wires to the neck.
You will use a handheld controller to turn the DBS system on and off. Your doctor will program the stimulator settings with a wireless device. The stimulation settings can be adjusted as your condition changes over time.
Most people don’t feel the stimulation as it reduces their symptoms. However, some people may feel a brief tingling sensation when the stimulator is first turned on.
It’s important to remember that essential tremor is progressive, and symptoms get worse over time. It is likely that you may need further programming in the future. See your neurologist or neurosurgeon when your condition changes.
Radiosurgery treatment of ET is an outpatient procedure in which highly focused radiation beams are used to destroy overactive cells that cause tremor. Radiation is delivered with pinpoint accuracy to the target, a small area in the thalamus called the ventral intermediate (VIM) nucleus (Fig. 3). The procedure is painless has few, if any, side effects.
Figure 3. During radiosurgery, a high dose of radiation is delivered to a portion of the thalamus. Over time the radiation will damage the nerve cells and interrupt the signals causing tremor.
The two main technologies are the Leksell Gamma Knife and linear accelerator systems such as the BrainLab Novalis. A stereotactic head frame or facemask is attached to the patient’s head to precisely localize the target area on an MRI scan and to hold the head perfectly still during treatment. Highly focused beams of radiation are delivered to the thalamus.
Radiation works by damaging DNA inside cells, making them unable to divide and grow. Patients typically experience a reduction in tremor a few months after treatment.
The surgical decision
Seek treatment at a center that offers significant experience, a team approach, and the full range of treatment options, including medication, surgery, and rehabilitation (physical, exercise, voice, balance).
Surgeries for essential tremor are performed by a neurosurgeon who has specialized training in functional neurosurgery.
The timing of when to consider surgery is different for each patient. If you have tremor despite optimal medications, then surgery should be considered. The type of surgery chosen will depend on your medical condition and personal needs. You and your physician can discuss which option is best for you.
Unlike other surgeries, such as pallidotomy, thalamotomy, or radiosurgery, DBS does not damage the brain tissue. Thus, if better treatments develop in the future, the DBS procedure can be reversed. (Three companies have FDA approval to manufacture DBS devices. Ask your physician about which one is best for you.)
Only the side that is most affected is treated first. Then it is up to the patient and physician to decide if the other side is to be operated on in the future.
What are the results?
Successful DBS is related to 1) appropriate patient selection, 2) appropriate selection of the brain area for stimulation, 3) precise positioning of the electrode during surgery, and 4) experienced programming and medication management. DBS for essential tremor may significantly reduce hand tremor in 60% to 90% of patients and may improve head and voice tremor.
Patients report other benefits of DBS. For example, better sleep, more involvement in physical activity, and improved quality of life.
Living with DBS
Once the DBS stimulator has been programmed, you are sent home with instructions for adjusting your own stimulation. The handheld controller allows you turn the stimulator on and off, select programs, and adjust the strength of the stimulation. Most patients keep their DBS system turned on 24 hours day and night. Some patients with essential tremor can use it during the day and turn off the system before bedtime. Your doctor may alter the settings on follow-up visits if necessary.
If your DBS has a rechargeable battery, you will need to use a charging unit. On average charging time is 1 to 2 hours per week. You will have a choice of either a primary cell battery or a rechargeable unit and you should discuss this with you surgeon prior to surgery.
Just like a cardiac pacemaker, other devices such as cellular phones, pagers, microwaves, security doors, and anti theft sensors will not affect your stimulator. Be sure to carry your Implanted Device Identification card when flying, since the device is detected at airport security gates.
Sources & links
If you have any questions, please call Mayfield Brain & Spine at 513-221-1100 or 800-325-7787.
basal ganglia: a mass of nerve cell bodies (gray matter) located deep within the white matter of the cerebrum. Has connections with areas that subconsciously control movement.
electrode: a conductor that carries electrical current.
pallidotomy: a surgical procedure that destroys the nerve cells in the globus pallidus of the brain. Used to treat the symptoms of rigidity and tremor.
stereotactic: use of three-dimensional coordinates to precisely locate deep brain structures.
thalamus: a relay station for all sensory messages that enter the brain; part of the basal ganglia.
thalamotomy: a surgical procedure that destroys the nerve cells in the thalamus of the brain. Used to treat the symptoms of tremor or pain.
updated > 1.2018
reviewed by > George Mandybur, MD, Mayfield Clinic, Cincinnati, Ohio
Mayfield Certified Health Info materials are written and developed by the Mayfield Clinic. We comply with the HONcode standard for trustworthy health information. This information is not intended to replace the medical advice of your health care provider.
90,000 Nervous tics and tremors of the hands: treatment and diagnosis
Initial appointment with a neurologist: 1850 rub.
The main causes of ticks are:
- chronic stress,
- hereditary factors,
- traumatic circumstances,
- head injury,
- taking medications,
- carbon monoxide poisoning.
From time to time we notice a noticeable tremor of the hands in ourselves or those close to us. This usually happens when experiencing bouts of fear or overwork, stress. A similar condition can be observed due to the intake of any pharmacological drugs. Involuntary body movements are especially noticeable when a person picks up something or stretches out his hand, pointing at something. This conversion disorder may be the first symptom of Parkinson’s disease. This means that hand tremors treatment should be trusted only by qualified specialists!
What is the reason for this pathology? There are many answers to this question.Here are some of them: depression, excessive physical (or emotional) stress, damage to the structures of the subcortex of the brain, genetic predisposition. Loss of control over certain muscle groups can occur with the abuse of coffee, tea, and alcoholic beverages.
MC “Pulse” will help you get rid of hand tremors and nervous tics. Treatment takes place in the shortest possible time: after all, it is carried out by the best doctors using the latest equipment and proven techniques. We will return your health!
If you have hand tremors, treatment should be started as soon as possible! A qualified specialist will help you understand the cause of such a disorder, and you will forget about this problem!
Another type of involuntary muscle contraction is a nervous tic.It arises from erroneous commands from the brain. According to statistics, nervous tics are most common in adults. The treatment of such pathologies depends on the twitching zone and the factors of the onset of the disease. Twitching of the facial muscles and uncontrolled movements of the eyelids require different therapies. Nervous tic treatment is primarily aimed at restoring the balance of the nervous system.
The Pulse Medical Center has been treating various types of conversion disorders for more than ten years.Professional psychotherapists practice the latest methods of examination and therapy to achieve maximum results! They diagnose nervous tics in adults, treatment will be quick and effective! At your service – homeopathy, SPA procedures, massage, pharmacotherapy. Nervous tic (treatment) , tremor – these conversion disorders will no longer bother you!
Call us or sign up online right now!
90,000 Diabetes mellitus.Review,
12 February 2016
Diabetes mellitus is a disease in which the body cannot control the level of sugar (glucose) in the blood. Blood glucose provides the body with energy to carry out daily human activities. The liver converts the food we consume into glucose, which then goes into the bloodstream.
In a healthy person, blood glucose levels are regulated by several hormones. Primarily insulin. Insulin is produced by the pancreas, a small organ that sits between the stomach and liver.The pancreas also produces other very important enzymes that enter the intestines to help digest food. Insulin allows glucose into the cells of the body, where it is used as an energy source.
People with diabetes either do not produce insulin (type 1 diabetes), or insulin cannot work properly (type 2 diabetes), or a combination of the two, which occurs in some forms of diabetes. In diabetes, blood glucose cannot enter cells efficiently, so blood glucose levels rise.This causes the cells to starve due to the lack of fuel that provides glucose, and the increased glucose levels damage organs and tissues.
Type 1 diabetes mellitus (T1DM) – insulin stops being produced, or it is not produced enough to regulate blood glucose levels. Type 1 diabetes mellitus affects 10% of diabetics. T1DM is usually diagnosed during childhood or adolescence. It is often referred to as diabetes of young people or insulin-dependent diabetes.
T1DM also occurs in older people with the destruction of the pancreas by alcohol, or its removal by surgery. It is also the result of progressive damage to pancreatic beta cells, the only cell type that produces significant amounts of insulin. People with type 1 diabetes mellitus need insulin treatment daily to maintain life.
Type 2 diabetes (T2DM). Although the pancreas still produces insulin, the body is partially or completely unable to use it.This is called insulin resistance. The pancreas secretes more and more insulin in an effort to overcome insulin resistance. These individuals develop type 2 diabetes when they are unable to produce enough insulin to overcome their insulin resistance. 90% of people with diabetes have type 2 diabetes . T2DM is usually diagnosed in adults over 45 years of age. Previously, this type of diabetes was called adult diabetes or non-insulin dependent. This name is no longer used because T2DM occurs in young people, and some people with T2DM require insulin therapy.Type 2 diabetes is usually controlled with diet, weight loss, exercise, and pills. However, about 50% of people with T2DM require insulin therapy from time to time.
Gestational diabetes (GDM) is a form of diabetes that can occur in women in the second half of pregnancy. Although gestational diabetes usually resolves after childbirth, a woman who has had it has a greater risk of developing type 2 diabetes in later years than women without a history of GDM.Women with GDM usually give birth to babies that are overweight.
Metabolic syndrome (also called syndrome X) is a type of disorder in which insulin-resistant diabetes (T2DM) is almost always accompanied by hypertension (high blood pressure), increased blood lipids (increased triglycerides, low-density lipoprotein (LDL), decreased high-density lipoproteins) (HDL), central obesity, clotting disorders and infectious defenses Metabolic syndrome increases the risk of cardiovascular disease.
Prediabetes is a common condition associated with diabetes. In persons with prediabetes, blood glucose levels are higher than normal, but not sufficient to make a diagnosis of diabetes. Prediabetes raises the risk of type 2 diabetes , heart disease, or stroke. Prediabetes can be cured without medication and insulin, with lifestyle changes, weight loss, and increased physical activity. Weight loss can prevent or at least delay the onset of type 2 diabetes.
The International Committee of the American Diabetes Association has revised the criteria for prediabetes by lowering blood sugar cut-off points for the diagnosis of prediabetes. About 20% of adults are likely to have this condition and the risk of developing diabetes in the next 10 years if they do not make lifestyle changes, increase physical activity, and maintain a healthy body weight.
The incidence of diabetes is growing rapidly. This increase is due to many factors, but most important is the high prevalence of sedentary obesity.
Complications of diabetes
Both type 1 and type 2 diabetes ultimately lead to high blood sugar levels, a condition called hyperglycemia. Long-term hyperglycemia damages the retina, blood vessels of the kidneys, nerves, and other blood vessels.
Damage to the retina in diabetes (diabetic retinopathy) is the leading cause of blindness.
Kidney damage from diabetes (diabetic nephropathy) is the leading cause of kidney failure.
Nerve damage from diabetes (diabetic neuropathy) is a leading cause of foot wounds and ulcers that often result in amputations.
Damage to the nerves of the autonomic nervous system can lead to gastric paralysis (gastroparesis), chronic diarrhea and an uncontrolled increase in heart rate and blood pressure.
Diabetes accelerates atherosclerosis (the formation of fatty plaques in the arteries), which can lead to blockages or blood clots…. These changes can lead to heart attack, stroke, and decreased circulation to the arms and legs (peripheral vascular disease).
Diabetes predisposes to high blood pressure, high cholesterol and triglyceride levels. These conditions, both on their own and together with hyperglycemia, increase the risk of cardiovascular disease, kidney disease, and other blood vessel complications.
Diabetes can contribute to a number of acute medical problems.Many infections are associated with diabetes, and they are often more dangerous for people with diabetes because they have impaired the body’s ability to fight infections. The problem is compounded by the fact that infection impairs glycemic control, which in turn results in delayed recovery from infection.
Hypoglycemia, or low blood sugar, occurs occasionally in most people with diabetes. This can be the result of using an excessive dose of a diabetic drug or insulin, skipping meals, or increased physical activity.It is very important to be able to recognize hypoglycemia and treat it from time to time. Headache, dizziness, hand tremors, sweating are common symptoms of hypoglycemia. You may feel severe weakness or cramps if your blood sugar is too low.
Diabetic ketoaziosis (DKA) is a serious complication in which uncontrolled hyperglycemia (usually due to a lack of insulin or a relative lack of insulin) over time leads to the accumulation of ketones (a metabolic product of fatty acids) in the blood.High ketone levels can be very dangerous. DKA is commonly found in streets with type 1 diabetes with inadequate blood sugar control. Diabetic ketoacidosis can be triggered by infection, stress, trauma, missed medications (such as insulin), or emergencies like stroke, heart attack.
Hyperosmolar hyperglycemic (non-ketoacidotic) syndrome is a serious condition in which blood sugar rises very high. The body tries to get rid of the excess sugar by eliminating it in the urine.The increase in the amount of urine is significant, and often leads to dehydration to such a degree that convulsions, coma, and even death appear. This syndrome usually occurs in people with type 2 diabetes who do not control their blood sugar levels, or are dehydrated, stressed, have an injury or stroke, or are on drugs such as steroids.
Assessment of tremor in Parkinson’s disease from the point of view of the theory of muscle spindles
Since K.N. Tretyakov  it is believed that the death of dopamine-producing neurons in the substantia nigra of the midbrain is the cornerstone of Parkinson’s disease [7, 12, 13, 20-22, 26, 28].Deficiency of cerebral dopamine leads to the fact that the caudate nucleus does not receive dopamine through the nigrostriatal pathway and the inhibitory premotor-caudato-pallido-thalamotor ring does not work. Excessive, i.e. impulses that are unnecessary at the moment for the activity of the brain, coming from the receptor fields of the body, are not inhibited and become pathological [6, 7, 20, 21]. It arrives in the cerebral cortex, and then along the descending extrapyramidal pathways, including the rubro-reticulospinal and nigro-reticulospinal, reaches g-motor neurons and realizes, in particular, tremulous hyperkinesis.The details of this general scheme will be clarified after presentation of the literature and clinical and neurophysiological data.
It is known that in each large muscle fibers of three types are distinguished: I, IIA, IIB [5, 14]. Slow tonic extrafusal muscle fibers of type I are innervated by tonic α-motor neurons; fast phasic extrafusal oxidative muscle fibers of type IIA are controlled by phasic α-motor neurons; ultrafast and most powerful phasic extrafusal glycolytic muscle fibers of type IIB receive innervation from the largest phasic α-motor neurons.All of the listed types of tonic and phasic α-motoneurons have independent (autonomous) innervation due to various groups of fibers in the pyramidal pathway.
Slow nuclear-burst intrafusal muscle fibers are controlled mainly by dynamic γ-motoneurons, which control the dynamic stage of muscle contraction, at which a change in muscle length occurs. Dynamic γ-motoneurons are probably innervated by the nigroreticulospinal pathway. Fast nuclear chain intrafusal muscle fibers are controlled mainly by static γ-motor neurons, which control the static phase of muscle contraction, in which the muscle length remains constant, for example, during isometric contraction.Static γ-motoneurons, in turn, receive innervation, apparently, from the rubro-reticulospinal pathways.
The influence of γ-motoneurons and the extrapyramidal system as a whole on α-motoneurons is carried out along the monosynaptic pathway 1a from muscle spindles to tonic or phasic α-motor neurons. γ-Motor neurons, muscle spindles, pathway 1a and α-motor neurons form a g-loop, which is the anatomical basis of the myotatic reflex, or servo-mechanism [4, 10, 11, 17], which plays a key role in the formation of muscle tone and control of voluntary and involuntary, including violent movements.
The aim of the work is to evaluate the tremor-rigid form of Parkinson’s disease from the point of view of the theory of muscle spindles.
Material and methods
153 patients with tremor-rigid form of Parkinson’s disease underwent 197 stereotaxic operations with a relatively favorable course. 3rd and 4th stages of the disease according to E.I. Candel  with a prescription of 6 years or more, as well as the 1st and 2nd stages, regardless of the duration of the disease, were given grounds to diagnose a relatively favorable course of the disease with slow progression.
Ventrolateral nuclear complex of the thalamus, fields H1, H2 of Forel, undefined zone served as stereotactic targets. Complete and almost complete cessation of tremor was achieved in 137 patients. The best results (95% complete elimination or significant reduction of tremor) were obtained in the group of men with a relatively favorable course of Parkinson’s disease.
Electromyographic (EMG) study (Medicor electromyograph) using cutaneous electrodes was performed in 33 patients before surgery and 14 after.As a control to compare EMG parameters in dynamics, we used EMG parameters of muscles on the “healthy” side in hemiparkinsonism. The distal (superficial finger flexor) and proximal (biceps brachii) flexors of the arm were examined, and the common extensor of the fingers was examined as an extensor muscle. EMG was recorded in resting mode and during functional tests (inhalation, synergy, contraction and extension of the studied muscle, contraction of the antagonist).
Results and discussion
The EMG amplitude reflects the quantitative aspect of involuntary excitation of phasic α-motor neurons [8, 9, 16].Rice. 1
|Fig. 1. Amplitude of EMG (in μV) of the flexor digitorum at rest and during functional tests.|
|Note. Here and in Fig. 2: black bars – control on the “healthy” side, white – on the side of hemiparkinsonism before surgery, gray – on the side of hemiparkinsonism after surgery.|
demonstrates the dynamics of the EMG amplitude of the superficial flexor muscle before and after surgery.At rest, the EMG amplitude (84 ± 27-104 ± 21 μV) showed the power of involuntary excitation of phasic α-motoneurons and exceeded (p <0.01) similar indicators of control studies. In respiratory and synergistic tests, the height of oscillations in the flexors (95 ± 41-170 ± 42 µV) exceeded (p <0.01) similar control indicators, as well as the amplitude indicators of the same muscles obtained in a state of physiological rest (Table 1).
A particularly high increase in the EMG amplitude was obtained on proprioceptive stimulation.With passive stretching of the biceps muscle (flexor) of the shoulder, the EMG amplitude of the biceps was sharply increased (p <0.01) - up to 295 ± 73 μV. Passive biceps stretch is closest to direct spindle stimulation. Flexor reciprocity coefficient, calculated by I.G. Okhnyanskaya and A.A. Komarova  was 121 ± 27% and showed a violation of the reciprocal relationship between flexors and extensors.
The amplitude of the EMG of the extensor digitorum at rest was 121 ± 31 μV, exceeding the analogous indices of the control and flexor muscles.A deep breath and synergy were accompanied by an increase in the oscillation height up to 180 ± 40 μV. The reciprocity coefficient was 75 ± 21%, indicating that there are no gross violations of the coordination relationship with the flexors on the extensor side.
In general, the assessment of EMG amplitudes indicated a high level of involuntary excitation of phasic α-motor neurons of the flexors (see Fig. 1) and extensors, as well as the sensitivity of α-motor neurons to functional tests, especially proprioceptive stimulation and passive stretching of the biceps.These facts seem to indicate the key role of muscle spindles in the realization of tremor. In addition, a violation of the coordination relations between the antagonists, especially on the flexor side, was revealed, which can be explained by excessive irritation of the secondary endings of the spindle, which facilitate the α-motor neurons of their own flexors and inhibit the α-motor neurons of the extensors.
EMG reflection of tremor is burst activity [15, 19, 23, 27, 29]. The volley discharge, diverted from the superficial flexor of the fingers at rest, lasted 62 ± 7 ms and reflected the time of involuntary excitation of phasic α-motor neurons (Table 1).2).
The salvo consisted of 5 ± 0.3 oscillations. Each oscillation reflects the action potential of 2-3 motor units [8, 9]. The duration of one oscillation, according to our data, was 13 ± 0.8 ms. The duration of the action potential of one phasic motor unit of the finger flexor in the trembling-rigid form of Parkinson’s disease is 6.60 ± 0.55 ms . The pause between volleys lasted 125 ± 7 ms and corresponded to the period of inhibition of phasic α-motoneurons or the impossibility of their excitation according to the “all or nothing” law.After the excitation phase, the neuron is immersed in a state of hyperpolarization and does not respond to signals coming from the spindles along the pathway 1a for about 80 ms . According to the hypothesis of H. Hufschmidt , in Parkinson’s disease there is an extended phase of hyperpolarization, which determines the duration of the pause between volley discharges of 125 ± 7 ms.
It is of interest to analyze the EMG amplitude during pauses between burst discharges (Fig. 2).
|Fig. 2. Amplitude of EMG (in μV) of the flexor during pauses between bursts of fingers – at rest and during functional tests.|
The height of the oscillations at rest was 17.3 ± 1.43 – 25.83 ± 4.28 μV in the flexor and 22 ± 3.16 μV in the extensor of the fingers, which is comparable to the EMG values on the “healthy” side. In respiratory and synergistic tests, there was a tendency to an increase in the EMG amplitude, with rare exceptions, but the increase in amplitude was less noticeable than in control studies. This means that neurons with less excitability reacted to intero- and proprioceptive stimulation than in control studies.During voluntary contraction and contraction of the antagonist, a significant (p <0.01) increase in the EMG amplitude was observed up to 30.8 ± 6.54-46.41 ± 16.13 μV in the flexors and 42.92 ± 7.63-48.27 ± 5.72 μV in the extensor. Passive stretching of the biceps did not change the EMG amplitude compared to the resting state.
Voluntary muscle contraction in Parkinson’s disease differs in that the phasic α-motor neurons are simultaneously affected by involuntary excitation from the spindle along the pathway 1a and voluntary stimulation coming along the pyramidal axons.At the moment of a salvo discharge, there is a summation of involuntary and voluntary excitation of phasic α-motoneurons. During the pause between volleys, the phasic α-motoneurons participating in the formation of the discharge are in a state of hyperpolarization and do not respond to both voluntary and involuntary stimuli. However, as shown above, motoneurons show some activity during the pause between volleys (see Fig. 2). The pause between discharges characterizes the functional state of α-motoneurons that are not involved in the formation of volley discharges, which include tonic and phasic α-motor neurons that retain normal innervation from the suprasegmental structures and do not participate in the formation of tremor.A slight increase in the EMG amplitude during functional tests during a pause between volleys indicates a small number of such motor units.
It cannot be ignored that static γ-motoneurons, after excessive excitation, must go through a phase of hyperpolarization, during which they do not respond to excessive impulses coming along the reticulo-rubrospinal pathways. In this case, the hyperpolarization of γ-motoneurons becomes a decisive factor for the termination of the salvo discharge on EMG, as well as the occurrence and maintenance of a pause between salvo discharges.Prolonged hyperpolarization can be explained by the partial addition of the periods of hyperpolarization of static γ-motor neurons and phasic α-motor neurons. We are talking about a partial addition of these periods: since the period of neuron hyperpolarization lasts 80 ms , the doubled period of hyperpolarization of α- and γ-motoneurons would be 160 ms, but in reality the pause between discharges lasts 125 ± 7 ms. In this case, the phase of hyperpolarization does not coincide in time for static γ-motor neurons and phasic α-motor neurons, namely, γ-motor neurons enter the phase of hyperpolarization and leave it earlier than α-motor neurons.After the end of the hyperpolarization phase for the static γ-motor neuron, it is able to respond to excessive impulses coming along the reticulo-rubrospinal pathway, which leads to a contraction of the nuclear chain intrafusal fiber and restores the discrepancy in the length between the intra- and extrafusal muscles, since the intrafusal fiber is already contracted, and extrafusal – still relaxed under the influence of hyperpolarization of phasic α-motor neurons. In Parkinson’s disease, synchronous and almost simultaneous excessive excitation of the pool of static γ-motor neurons should occur, after which the same motor neurons simultaneously appear in the phase of hyperpolarization.
The specified mode of excitation and inhibition is transmitted to phasic α-motoneurons, as a result of which volley discharges are diverted from the phasic oxidative muscle fiber with pauses between them. Perhaps this is due to the simultaneous shutdown of the inhibitory function of the corresponding pool of neurons in the caudate nucleus and the functional properties of the static γ-motoneurons themselves. After the end of the phase of hyperpolarization for the phasic α-motor neuron, it restores the state of polarization and is able to respond to signals that come along path 1a from the spindles of the muscle it innervates.By this time, the intrafusal fiber is already contracted, and the extrafusal fiber is still relaxed. Conditions arise for the next salvo discharge.
It is impossible not to take into account other inhibitory spinal reflexes, in particular, autogenous inhibition from the Golgi tendon receptors and return – through the corresponding collateral. These inhibitory reflexes are capable of weakening excessive excitation of α-motoneurons and involuntary muscle contraction, while the decisive contribution to the termination of the burst discharge belongs to the mechanism of neuronal hyperpolarization, which also determines the duration of the pause between burst discharges.In maintaining this pause, inhibition by the spindles of the antagonist may play a role, since at the moment of the pause in the agonist muscle, the antagonist produces a volley discharge. If we take into account that the pause between flexor bursts of 125 ± 7 ms is almost twice as long as the 69 ± 8 ms extensor burst discharge (see Table 2), it becomes clear that the reciprocal inhibition mechanism cannot provide such a long pause between flexor bursts. Consequently, the decisive role in the occurrence and maintenance of a pause between burst discharges belongs to the mechanism of prolonged hyperpolarization of phasic α-motor neurons.In addition, in our series of observations, there were single records when volley activity was diverted from the flexor of the fingers, and there were no volley discharges in the extensor of the fingers. A similar phenomenon is also cited by I.G. Okhnyanskaya and A.A. Komarova , B. Drechsler . In these cases, a pause between volleys in the flexor occurred without the involvement of the reciprocal mechanism and could be maintained due to prolonged hyperpolarization of α-motoneurons.
Respiratory and synergistic tests were accompanied by a significant (p <0.01) shortening of the pause between volleys in the flexor of the fingers in response to introceptive stimulation, which indirectly reflected an increase in excessive excitation of phasic α-motor neurons.The contraction of the flexor and its antagonist resulted in inhibition of volley activity in the flexor of the fingers, which resulted in a decrease in the number of recordings containing volleys from 17 at rest to 13 (see Table 2), as well as a shortening of the pause between volleys to 80 ± 9–88 ± 8 ms (p <0.01). Voluntary stimulation during flexor contraction was accompanied by the involvement of an additional pool of motor neurons that did not participate in the formation of volleys, and whose discharges partially filled the pauses between volleys. Contraction of the antagonist (extensor digitorum) led to reciprocal inhibition of the phasic α-motor neurons of the flexor, which also reduced the pauses between volleys.At the same time, the tremor rhythm increased to 7 ± 0.3 per second (p <0.01) compared to the state of rest.
It is interesting to compare the characteristics of the proximal and distal flexor of the arm, i.e. the biceps (flexor) of the shoulder and the superficial flexor of the fingers (see Table 2). At rest, in the biceps, there was an increase in the duration of one oscillation to 15 ± 0.7 ms (p <0.05) compared to the analogous index of the flexor of the fingers, which means an increase in the number of phasic muscle fibers involved in involuntary contraction, and does not contradict the idea that that the human proximal muscles have larger motor units than the distal ones.The duration of the action potential of one motor unit of the biceps in the tremulous-rigid form of Parkinson's disease is 7.3 ± 0.53 ms , respectively, the duration of one oscillation in the structure of a volley may include at least two motor units. The rest of the indices of the burst activity taken at rest from the proximal and distal flexors of the hand did not differ significantly.
Respiratory and synergistic tests in comparison with the state of rest were accompanied by an increase (from 5 to 9) in the number of recordings with salvo activity retracted from the biceps, while the number of oscillations in a salvo decreased from 5 ± 0.8 to 3 ± 0.4 (p < 0.05) due to a decrease in the number of involuntarily excited phasic α-motor units against the background of a shortening of the salvo discharge from 65 ± 0.6 s to 53 ± 9 - 57 ± 0.5 ms.During deep inspiration, the duration of one oscillation also decreased from 15 ± 0.7 to 13 ± 1 ms (p <0.05), apparently due to a decrease in the number of muscle fibers subjected to involuntary contraction. The duration of the pause between volleys did not change significantly.
The voluntary contraction of the biceps was accompanied by an increase in the number of recordings with salvo activity from 5 to 8 and an increase in the duration of one oscillation from 15 ± 0.7 to 16 ± 0.01 ms (p <0.05), which meant an increase in the number of contracted muscle fibers involved in a salvo discharge, probably due to the additionally included motor units.This is not contradicted by the tendency to lengthen the salvo discharge to 75 ± 8 ms, but the number of oscillations in the salvo tended to decrease to 4 ± 0.4. The pause between bursts was reduced to 87 ± 11 ms (p <0.02), which was not contradicted by an increase in the tremor rhythm to 7 ± 0.3 bursts per second.
Compared with the flexor of the fingers in the extensor, there was a tendency to lengthening the volley discharge, shortening the pause between volleys, and decreasing the duration of one oscillation (see Table 2). There was an increase in the tremor rhythm up to 7 ± 0.4 in 1 s (p <0.01).During inspiration, compared with the resting state, one oscillation was lengthened to 12 ± 0.05 ms (p <0.05) due to an increase in the number of involuntarily contracted phasic muscle fibers against the background of a tendency to lengthen the volley discharge to 76 ± 6 ms. The number of oscillations in a salvo increased to 6 ± 0.6 (p <0.05) due to an increase in involuntarily excited phasic motor units. The pause between volleys tended to increase up to 106 ± 9 ms. The rhythm of salvo discharges decreased to 6 ± 0.4 (p <0.05).
Consequently, the duration of the volley discharge in the flexors is shorter, and the pause between volleys is longer than in the extensor.This fact testifies to the predominance of excessive excitation in the β-motoneurons of the extensors, probably due to the anti-gravitational load, which is also confirmed by the higher amplitude of the extensor EMG (see Table 1).
In isolated patients, volley activity was irregular. Its analysis is of interest, since irregular volley activity precedes the formation of regular volleys and makes it possible to clarify some of the features of tremor formation. Most often, it was withdrawn from the muscles of the arms of the flexor group.It is possible that the flexors, to a greater extent than the extensors, “oppose” the formation of burst activity. Most often, an irregular salvo activity was provoked by an arbitrary contraction of the agonist and especially the antagonist; most rarely, irregular volley discharges were diverted from the muscles in a state of physiological rest. Apparently, impulses from the spindles play a role in the origin of the volley discharges, since the contraction of the antagonist is accompanied by the stretching of the agonist, while the sensory endings of the spindle are irritated.This fact is not contradicted by the increase in the number of records with irregular salvo activity from the biceps during its passive stretching up to 4 versus 1 record at rest.
After the operation, the volley activity was eliminated, which objectively confirmed the elimination of trembling hyperkinesis. In isolated patients, irregular volley discharges were discharged from some muscles of the flexor group at rest, as well as during a respiratory test. The duration of the salvo discharge was 25-75 ms (tab.3).
Arbitrary contraction and contraction of the anatagonist provoked the most formalized volley activity in the flexor of the fingers. In this case, the volley discharge was reduced in time to 25-50 ms. The number of oscillations in the salvo ranged from 4 to 6, the duration of one oscillation did not exceed 8-12 ms, the pause between the volleys lasted 50-100 ms. The rhythm of salvo discharges increased to 7-11 per second, apparently due to the shortening of salvo discharges.
The most complete volley discharges were issued in the common extensor of the fingers. At rest, during inhalation and a synergistic test, they were shortened to 25 – 75 ms compared to the preoperative level, which corresponded to a decrease in the number of oscillations in a volley to three, which indicated a decrease in the number of motor units involved in the formation of a volley. The duration of one oscillation was 8-16 ms, the pause between bursts was 100 ms. The rhythm of the salvo discharges did not change after the operation. Contraction of the extensor digitorum of the fingers and its antagonist led to a shortening of one oscillation to 8 ms, the other indices of volley activity did not change significantly (see Fig.tab. 3).
Consequently, the restructuring of the residual salvo activity after the operation consisted in a shortening of salvo discharges, a decrease in the number of oscillations in a salvo, which indicated a decrease in involuntarily excited motor units. The tendency to shorten one oscillation indicated a decrease in the number of involuntarily contracted phasic muscle fibers involved in the formation of tremor. The worst of all, volley activity was eliminated in the extensor of the fingers, apparently due to a more precise response of the extensor muscles to the gravitational load.In addition, after the operation, both flexors and extensors more readily produced burst activity in response to voluntary contraction and contraction of the antagonist, which could indicate the predominant role of proprioceptors, i.e. spindles in the origin of the tremor. Attention was drawn to some similarity between irregular and residual volley activity after surgery.
After surgery, the amplitude of the EMG flexors at rest (13 ± 1.7-19 ± 0.4 μV) was significantly (p <0.01) less (see Table 1), which indicated a decrease in excess excitability of phasic α-motor neurons ...Respiratory and synergistic tests led to a significant (p <0.01) decrease in the height of oscillations to 17 ± 5.7—41 ± 25 µV compared with preoperative values, but they were higher than in the state of functional rest. Consequently, α-motor neurons retained the ability to respond to functional stimuli (see Fig. 1). An arbitrary contraction of the flexors and a test for the reciprocity of innervation did not cause a significant change in the EMG amplitude, which indicated the absence of postoperative paresis.
After the operation, the amplitude of the EMG of the extensors at rest significantly (p <0.02) decreased to 13 ± 3.7—38 ± 17 µV. A deep breath and synergy were accompanied by a decrease (p <0.01) in the height of the extensor oscillations to 21 ± 7–42 ± 23 µV. In comparison with the resting state, there was a tendency to an increase in the level of excitability of phasic α-motor neurons. Arbitrary contraction of the extensors themselves and contraction of their antagonists provoked a tendency towards some increase in the amplitude of the EMG extensors (see.tab. 1). The extensor reciprocity and adequacy ratios tended to decrease.
In general, the dynamics of the amplitudes of muscle potentials convincingly shows a decrease in involuntary excitation of phasic α-motor neurons and objectively confirms the therapeutic effect of surgical treatment.
On the basis of the presented data, a hypothesis of the origin of tremor is constructed, which can be used to understand other hyperkinesis [24, 25]. The energy base of hyperkinesis is natural afferent impulses from the receptive fields of the body, especially from proprioceptors, or muscle spindles.In the brainstem, part of this impulse is switched to the nuclei of the reticular formation and through nonspecific pathways as part of the ascending activating system reaches the associative cortex of the large brain, where it is used to maintain wakefulness and attention . It is known that in a state of sleep the ascending activating system is turned off, which is accompanied by the elimination of tremors and other hyperkinesis.
The waking brain removes excess nonspecific impulses along the inhibitory premotor-caudato-pallido-thalamomotor pathway (caudate loop), which functions according to the principle of negative feedback.Elimination of excess impulses is carried out at the level of the caudate nucleus with the help of dopamine, which enters the caudate nucleus via the nigrostriatal pathway. In Parkinson’s disease, the caudate loop does not fire due to a deficiency of cerebral dopamine. With Huntington’s chorea, torsion dystonia and athetosis, there is a primary nested lesion of the neurons of the caudate nucleus (“marble state”).
It should be assumed that there are populations of neurons in the caudate nucleus for selective autonomous action (control) on spindles belonging to either tonic type I, or oxidative phasic type IIa, or glycolytic phasic type IIb muscle fibers.This control is carried out via polysynaptic extrapyramidal pathways, including γ-motoneurons. As a result of damage to the caudate nucleus, excessive impulses are not extinguished and becomes hyperkinesogenic. On the way to the motor cortex through the caudate loop, it passes through the ventrolateral nuclear complex of the thalamus, which is proven by the elimination of hyperkinesis as a result of stereotaxic operations on the optic tubercle. Non-inhibitory excessive hyperkinesogenic impulses along the caudate loop enters the motor cortex, from where it follows the polysynaptic extrapyramidal pathways, including the cortical-cerebellopontine-dentate-rednuclear-reticulospinal pathways, etc., reaches γ-motoneurons .
It is believed that in Parkinson’s disease the control of static γ-motor neurons is selectively affected. Further, it is necessary to make the assumption that there is a simultaneous synchronous excessive excitation of a large pool of static γ-motoneurons. After excitation, the same pool falls into a state of hyperpolarization and does not respond to signals arriving along the reticulo-rubrospinal pathway. The specified synchronous excessive excitation of static γ-motoneurons and their subsequent synchronous immersion in the hyperpolarization phase is a key moment in terms of the spinal mechanisms of tremor.Excessive excitation of static γ-motoneurons leads to a contraction of the nuclear chain intrafusal muscle fibers belonging to the phasic oxidative extrafusal fibers of type IIa, then the servo mechanism is triggered, and the pathological signal is transmitted to the phasic α-motor neuron through the monosynaptic pathway 1a without distortion. The latter reduces the type IIA extrafusal muscle fiber, and a volley discharge occurs on the EMG, the characteristics of which are discussed in the text of the article.
Thus, at the spinal level, trembling hyperkinesis is realized by a myotatic unit with the participation of a static γ-motor neuron, a nuclear chain intrafusal fiber, pathway 1a, phasic α-motor neurons, and an oxidative extrafusal muscle fiber of type IIA.The hypothesis presented allows a deeper understanding of the pathogenesis of tremor, as well as to evaluate the results of surgical treatment.
Medical Center Axon
What is Parkinson’s disease.
The disease occurs in humans due to a violation of the production of a very important neurotransmitter hormone – dopamine.
The gradual decrease in hormone intake leads to the development of symptoms – from the most subtle to irreversible.
The development of dopamine deficiency gradually takes away from a person the ability to control his body.
Stages of Parkinson’s disease
Zero – the person has no symptoms of the disease.
First – minor movement disorders in the fingers or hand,
depression, fatigue, sleep disturbances are possible; the intermediate stage involves the concentration of tremor on a particular limb,
the tremor of which stops only during sleep.
Second – tremor and movement disorders are observed on both sides, facial expressions become poorer, sweating is disturbed – the skin becomes very dry or greasy; the person can still cope with ordinary affairs,
although his movements are noticeably slowed down.
The third stage – the face becomes mask-like, a posture is formed, which is often called the supplicant’s pose,
“puppet” walking appears, stiffness in movements and muscle stiffness.
Fourth – there is a pronounced inability to maintain balance, the work of the vestibular apparatus is disrupted (a person can fall when walking due to loss of balance),
is characterized by body movement by inertia, help is needed in everyday life. At this stage, dementia may join.
Fifth – pronounced disorders of the nervous system: a person cannot move independently, eat, control of urination is disturbed, hallucinations appear,
A person at this stage is completely dependent on the help of others, the words spoken by him are very difficult to understand.
Early symptoms of Parkinson’s disease
weak, imperceptible hand tremors appear; movements slow down slightly, especially small ones; facial expressions become more than 90,258 poor; possibly the development of depression, the appearance of insomnia, disruption of the gastrointestinal tract.
Causes of the disease
damage to the cells of the substantia nigra by free radicals, toxins; due to the transfer of encephalitis;
traumatic brain injury; vascular diseases of the brain; vitamin D deficiency; changes at the genetic level;
mutations leading to degeneration of brain cells; uncontrolled intake of antipsychotics, alcohol consumption
Drugs for the treatment of Parkinson’s disease:
Amantadine tablets are effective initially, which stimulates dopamine production.
At the first stage, dopamine receptor agonists (mirapex, pramipexole) are also effective.
The drug levodopa in combination with other drugs is prescribed in complex therapy at later stages of the development of the syndrome.
Exercise therapy and massage for Parkinson’s disease are also required
– circular movement with shoulders, hands;
– twisting while standing, sitting;
– tilting the head, stretching the neck;
– torso bending, bending in the lumbar region;
– Alternate leg lifts parallel to the floor.
– outdoor hiking; to control speech – reading books aloud, pronunciation of simple tongue twisters.
An ailment can significantly worsen the quality of life, but if you approach recovery responsibly,
then a person can engage in labor activities for many years after the diagnosis is made, and think purely.
Neurology in Izmailovo – MC Clinic
In the modern world, diseases of the nervous system are gaining momentum.According to statistics, more and more young people are faced with neurological disorders today, who cannot cope with constant stress and do not even notice how a dangerous pathology is developing. Untimely treatment of neurological abnormalities threatens with serious complications, and in severe cases, the patient’s disability is possible.
Experienced neurologists at our clinic will help not only get rid of existing diseases of the nervous system, but also prevent the development of complications and concomitant pathologies.For the treatment of patients with neurological diseases, we use the most modern methods of therapy, which are able to restore the patient’s health in a short time.
Indications for visiting a neurologist
Many patients do not take the obvious symptoms of neurological diseases seriously. They believe that headaches and other abnormalities are the result of overwork and do not require medical attention. However, experts insist that an urgent need to consult a doctor with the following primary symptoms:
- Headaches and sudden dizziness.
- Pain in the back and neck.
- Hand tremor not related to alcohol consumption.
- Head trembling.
- Lip or chin trembling.
- Sleep disturbances or insomnia.
- Increased muscle tone.
- Numbness in any part of the body.
- Decreased memory and concentration.
- A sharp decrease in vision or hearing for no apparent reason.
- Internal anxiety, tension.
People who lead a sedentary lifestyle, work at a computer, do nervous work and experience constant stress or depression should pay particular attention to their health. Patients who have suffered craniocerebral trauma, strokes and vascular crises, people diagnosed with osteochondrosis, chronic fatigue, Parkinson’s disease, etc.
A special feature of the treatment in our clinic is the high qualification of specialists, modern equipment and complete confidentiality.You can make an appointment with a neurologist in our clinic in the Izmailovo district by calling the registration numbers indicated on the website. Reception is conducted without breaks and days off.
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Experience of clinical use of asphatase alpha in a young patient with childhood hypophosphatasia | Kalinchenko
Hypophosphatasia is a rare genetic disorder with an autosomal recessive or dominant mode of inheritance caused by mutations in the ALPL gene encoding tissue nonspecific alkaline phosphatase (TNSALP).The ALPL gene, consisting of 12 exons, is located on chromosome 1 (1p36.1–34) . To date, more than 388 mutations have been described in various regions of the ALPL gene , which explains a wide range of clinical manifestations. According to estimates, the prevalence of the disease is 1: 100,000 – 1: 300,000 newborns .
Normally TNSALP hydrolyzes inorganic pyrophosphate, pyridoxal-5′-phosphate and phosphoethanolamine – the main inhibitors of hydroxyapatite crystal formation. A decrease in the enzymatic activity of TNSALP leads to the accumulation of its extracellular substrates , disrupting the processes of bone mineralization and the formation of hydroxyapatite crystals .Histomorphometry shows an increase in the volume of the osteoid, which contains a large amount of non-mineralized bone matrix without hydroxyapatite crystals, which leads to rickets and osteomalacia .
Depending on the age of onset of the disease, bone abnormalities diagnosed in utero, early tooth loss, short stature, craniosynostosis, rickets skeletal changes, muscle hypotension, vitamin B6-dependent convulsions can be observed [1, 5].
The only pathogenetic therapy for hypophosphatasia is lifelong enzyme replacement therapy of human recombinant TNSALP – asphotase alpha [6, 7], approved in 2015 by the US Food and Drug Administration (FDA) for the treatment of perinatal, infantile and childhood forms of hypophosphatasia in the United States [ 8, 9].In the same year, the drug was approved for use in clinical practice in Canada, Japan and Europe.
There are reports [10, 11] in the literature about the successful use of asphatase alpha in small groups of adult patients.
The article presents the first clinical experience of using a genetically engineered preparation of alkaline phosphatase – asphatase alpha in Russia in a young man from 17 to 18 years of age inclusive with a childhood form of hypophosphatasia.
Patient A.first applied to the National Medical Research Center of Endocrinology of the Russian Ministry of Health at the age of 17 with complaints of severe muscle weakness, tremors of the arms and legs, limitation of physical activity, inability to move independently – he walked with crutches. On examination, a keeled chest deformity, pronounced varus deformity of the hips, valgus deformity of the knee joints and lower legs, planovalgus placement of the feet, and kyphosis of the lumbar spine were noted (Fig. 1). Height 152 cm, weight 65 kg, BMI = 28.1 kg / m2.
Fig. 1. The appearance of a patient with hypophosphatasia.
Note : keeled deformity of the chest, varus deformity of the hips, planovalgus position of the feet.
From the anamnesis it is known that in the second year of life there was a deformity of the chest, there was a “duck gait” when walking by the hands, delayed motor development – did not walk independently until 2.5 years. The condition was regarded as vitamin D-dependent rickets, and received drug therapy with active metabolites of vitamin D, which led to a worsening of the condition.At the age of three, he suffered a fracture of the bones of the left leg, at the age of 5 – a fracture of the sacrum.
On examination at the age of 15: hallux valgus of the lower extremities, a decrease in the level of 25 (OH) D to 11.1 ng / ml (norm> 30), alkaline phosphatase – up to 20 U / l (norm 40-390), phosphorus – up to 0.77 mmol / l (norm 0.95-1.65) against the background of normal calcium levels and a slight decrease in parathyroid hormone. He noted pain in the legs and muscle weakness, repeated dislocations of the ankle joints. The combination of rickety changes in bone structure and low alkaline phosphatase levels served as the basis for the diagnosis of hypophosphatasia.
Upon admission to the hospital, the indicators of phosphorus-calcium metabolism are within the reference values, the alkaline phosphatase activity is reduced to 18 U / l. X-ray examination of the knee and ankle joints revealed multiple areas of bone loss and osteosclerosis, narrowing of the joint spaces, signs of chondrocalcinosis. Molecular genetic analysis revealed the presence of a compound heterozygous mutation in the ALPL gene c.302A> G / c.571G> A, which confirmed the diagnosis of hypophosphatasia.Both mutations have been described previously.
Considering the pronounced growth retardation (SDS -3.24), the presence of bone deformities, limitation of movement (pain in the legs and fatigue when walking, movement with support on crutches), tremor at rest and after physical exertion, the patient is indicated for therapy with asphotase alpha. Since the drug is not registered in Russia, the child’s father gave written consent to treatment with the study drug. The first injection was performed at the age of 17.9 years (07/23/2018).
After 5 months of therapy with asphotase alfa at a dose of 70 mg / day, significant positive dynamics were noted: a decrease in muscle tremor during walking, an increase in exercise tolerance, the ability to independently move without crutches at a distance of 86 meters according to the results of a 6-minute walk test.Considering that before the treatment, the patient’s movement was possible only with support on crutches, the effectiveness of therapy was assessed by the increase in the distance that the patient can walk on his own.
In the study of the state of the skeletal system, an increase in markers of bone remodeling was revealed: osteocalcin – 92.38 ng / ml (norm 24-70), C-terminal telopeptide of type I collagen – 1.39 ng / ml (norm 0.01-0.7 ). According to the results of multispiral computed tomography of the thoracic and lumbar spine, there is a pronounced kyphoscoliotic deformity with adhesion of the ribs to the pericardium of the right atrium (Fig.2).
Fig. 2. MSCT of the thoracic and lumbar spine.
Description: pronounced kyphoscoliotic deformity with adherence of the ribs to the pericardium of the right atrium.
In order to compensate for vitamin D deficiency in the hospital, therapy was carried out with a native vitamin D preparation – cholecalciferol in a total saturating dose of 200,000 IU. In the future, to maintain the optimal level of vitamin D, it was recommended to take colecalciferol at 10,000 IU / week.
At the time of the last observation, 6 months after initiation of therapy, the patient continues treatment with asphotase alfa at a dose of 70 mg / day 3 times a week. Against the background of the therapy, he subjectively feels the appearance of muscle strength, the desire to move, the tremor of the arms and legs completely disappeared, he can walk 100 meters on his own without support on crutches. The ALP content in the blood is 8864 U / L, which indicates the patient’s compliance and the effectiveness of the therapy. The only complication of the therapy is a local reaction in the form of hyperemia at the injection sites (Fig.3). This complication is common and, according to the literature, occurs in more than 90% of patients receiving treatment.
Fig. 3. Reactions at the sites of subcutaneous injection of asphatase alfa.
It was recommended to continue therapy with a genetically engineered preparation of alkaline phosphatase (asphotase alfa 70 mg / day 3 times a week) and native vitamin D (colecalciferol 10,000 IU / week) under the control of phosphorus-calcium metabolism once every 3 months.
Hypophosphatasia is a rare hereditary progressive rickets-like disease, first described in 1934 by B.Chown in siblings who died of a pathology then called “renal rickets” . In 1948, the Canadian pediatrician John C. Rathbun reported a three-year-old patient with bone fractures, severe growth retardation, convulsive syndrome, and a sharply reduced level of alkaline phosphatase in the blood .
Until recently, symptomatic therapy remained the only possible treatment for hypophosphatasia. Attempts to use intravenous infusions of plasma rich in soluble alkaline phosphatase from patients with Paget’s disease did not bring the desired result .Transplantation of allogeneic mesenchymal bone marrow stem cells also proved to be ineffective [14, 15]. In 2008, a qualitatively new drug was created with the laboratory code ENB-0040, Asfotase Alfa, registered in October 2015 in the United States . Based on successful preclinical trials in Alpl – / – mice [16, 17], clinical studies in humans have been carried out. Today, asphotase alfa is approved in many countries for the treatment of hypophosphatasia.
Asphotase alpha is a recombinant molecule with an IgG1 Fc domain and a carboxyterminal deca-aspartate site, which has a high affinity for hydroxyapatite crystals .The therapeutic effect is realized through the hydrolysis of inorganic pyrophosphate, a decrease in the accumulation of extracellular substrates TNSALP, which improves the mineralization of the skeleton.
The efficacy and safety of the drug was evaluated in prospective open multicenter clinical trials (NCT00952484, NCT01203826) in patients with perinatal, infantile and pediatric forms of hypophosphatasia . As the results of clinical studies accumulated, a significant improvement in mineralization, histological structure of bone tissue, an increase in the overall survival of patients during treatment with alpha asphotase was shown [19, 20].
Currently, there is evidence of the effectiveness of TNSALP enzyme replacement therapy in adolescents and adult patients with hypophosphatasia [10, 21]. The results of a five-year follow-up in the framework of a multicenter, randomized, open-label phase II trial (NCT01163149) of 19 patients, whose mean age was 55 years (13–66 years), indicate a significant positive trend in terms of bone mineralization, a decrease in extracellular substrates TNSALP, improved motor activity and quality of life of patients, reduction of pain syndrome when using the drug in doses of 0.3 mg / kg / day or 0.5 mg / kg / day, followed by an increase to 1 mg / kg / day subcutaneously 6 times a week.The most common adverse events were injection site reactions, including erythema, pain, edema and pruritus, which did not require interruption of treatment.
In Russia, asphotase alfa was first used in 2015 in the treatment of two patients with infantile and pediatric forms of hypophosphatasia at the age of 6 months and 7 years, respectively , but there were no reports of the use of the drug in adult patients with a pediatric form in our country. In the presented clinical case, given the development of various complications of this disease, the progressive disability of the patient, the increased risk of mortality in relation to the general population, the council and the Medical Commission of the National Medical Research Center of Endocrinology of the Ministry of Health of Russia made a decision on therapy with a genetically engineered preparation of alkaline phosphatase.Against the background of continuous treatment with asphotase alpha for six months, a stable positive effect was noted – an objective clinical improvement, an increase in the patient’s quality of life, and the achievement of adequate control over the disease. Over the entire observation period, no significant side effects, except for local reactions, were observed.
Taking into account the lack of experience in the treatment of adult patients with asphotase alfa in the Russian Federation, further regular medical observation and monitoring of biochemical parameters is necessary.
The described clinical case clearly demonstrates the severity of the course of the disease in the absence of timely diagnosis and correction of violations. Based on data from foreign literature , despite a small number of studies, therapy with human recombinant TNSALP – asphotase alpha, unregistered in our country, was initiated. The present case demonstrates the effectiveness of initiation of therapy with asphotase alpha even in the case of late diagnosis.Against the background of treatment, already after 5 months, a patient at the age of 18 showed a decrease in pain syndrome, an increase in motor activity and a decrease in tremor, which was not accompanied by any undesirable phenomena except for redness at the injection site and the positive effect of treatment persisted for even subsequent 3 months of observation. However, further studies are needed to confirm the efficacy and safety of long-term use of TNSALP enzyme replacement therapy in patients with hypophosphatasia of all age ranges.
Patient Consent . The patient voluntarily signed an informed consent for the publication of personal medical information in anonymized form in the journal “Osteoporosis and Osteopathy”.
Conflict of interest . The authors declare no obvious and potential conflicts of interest related to the publication of this article.
1.Whyte MP. Hypophosphatasia – aetiology, nosology, pathogenesis, diagnosis and treatment. Nature Reviews Endocrinology. 2016; 12 (4): 233-246. doi: https://doi.org/10.1038/nrendo.2016.14
2. Sesep.uvsq, fr / 03 [Internet]. Mornet E. The tissue nonspecific alkaline phosphatase gene mutations database. Accessed date: 10 February 2019. Available from: http://www.sesep.uvsq.fr/03_hypo_mutations.php. 2019.
3.Mornet E. Hypophosphatasia. Orphanet J. Rare Dis. 2007; 2 (1). doi: https://doi.org/10.1186/1750-1172-2-40
4. Addison WN, Azari F, Sørensen ES, et al. Pyrophosphate Inhibits Mineralization of Osteoblast Cultures by Binding to Mineral, Up-regulating Osteopontin, and Inhibiting Alkaline Phosphatase Activity. J. Biol. Chem. 2007; 282 (21): 15872-15883. doi: https://doi.org/10.1074/jbc.M701116200
5.Orimo H. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa. Ther. Clin. Risk Manag. 2016: 777. doi: https://doi.org/10.2147/tcrm.s87956
6. Whyte MP, Greenberg CR, Salman NJ, et al. Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia. N. Engl. J. Med. 2012; 366 (10): 904-913. doi: https://doi.org/10.1056/NEJMoa1106173
7.Whyte MP, Rockman-Greenberg C, Ozono K, et al. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J. Clin. Endocr. Metab. 2016; 101 (1): 334-342. doi: https://doi.org/10.1210/jc.2015-3462
8. Alexion.com [Internet]. FDA Approves StrensiqTM (asfotase alfa) for Treatment of Patients with Perinatal-, Infantile- and Juvenile-Onset Hypophosphatasia (HPP). Available from: https: // alexion.com / Documents / Strensiq_USPI.
9. Scott LJ. Asfotase Alfa in Perinatal / Infantile-Onset and Juvenile-Onset Hypophosphatasia: A Guide to Its Use in the USA. Biodrugs. 2016; 30 (1): 41-48. doi: https://doi.org/10.1007/s40259-016-0161-x
10. Remde H, Cooper MS, Quinkler M. Successful Asfotase Alfa Treatment in an Adult Dialysis Patient With Childhood-Onset Hypophosphatasia.Journal of the Endocrine Society. 2017; 1 (9): 1188-1193. doi: https://doi.org/10.1210/js.2017-00307
11. Freitas TQ, Franco AS, Pereira RMR. Improvement of bone microarchitecture parameters after 12 months of treatment with asfotase alfa in adult patient with hypophosphatasia. Medicine. 2018; 97 (48): e13210. doi: https://doi.org/10.1097/md.0000000000013210
12.Macfarlane JD, Kroon HM, van der Harten JJ. Phenotypically dissimilar hypophosphatasia in two sibships. Am. J. Med. Genet. 1992; 42 (1): 117-121. doi: https://doi.org/10.1002/ajmg.1320420124
13. Rathbun JC. “Hypophosphatasia”. Am. J. Dis. Child. 1948; 75 (6): 822. doi: https://doi.org/10.1001/archpedi.1948.02030020840003
14.Whyte MP, Valdes R, Ryan LM, McAlister WH. Infantile hypophosphatasia: Enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease. The Journal of Pediatrics. 1982; 101 (3): 379-386. doi: https://doi.org/10.1016/s0022-3476(82)80061-9
15. Whyte MP, Kurtzberg J, McAlister WH, et al. Marrow Cell Transplantation for Infantile Hypophosphatasia.J. Bone Miner. Res. 2003; 18 (4): 624-636. doi: https://doi.org/10.1359/jbmr.2003.18.4.624
16. Tadokoro M, Kanai R, Taketani T, et al. New Bone Formation by Allogeneic Mesenchymal Stem Cell Transplantation in a Patient with Perinatal Hypophosphatasia. The Journal of Pediatrics. 2009; 154 (6): 924-930. doi: https://doi.org/10.1016/j.jpeds.2008.12.021
17.Millán JL, Narisawa S, Lemire I, et al. Enzyme Replacement Therapy for Murine Hypophosphatasia. J. Bone Miner. Res. 2007; 23 (6): 777-787. doi: https://doi.org/10.1359/jbmr.071213
18. Yadav MC, Lemire I, Leonard P, et al. Dose response of bone-targeted enzyme replacement for murine hypophosphatasia. Bone. 2011; 49 (2): 250-256. doi: https://doi.org/10.1016/j.bone.2011.03.770
19.Bowden SA, Foster BL. Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy. Drug Des. Devel. Ther. 2018; Volume 12: 3147-3161. doi: https://doi.org/10.2147/dddt.s154922
20. Whyte MP, Madson KL, Phillips D, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016; 1 (9). doi: https://doi.org/10.1172/jci.insight.85971
21.Whyte MP, Simmons JH, Moseley S, et al. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. The Lancet Diabetes & Endocrinology. 2019; 7 (2): 93-105. doi: https://doi.org/10.1016/s2213-8587(18)30307-3
22. Kishnani PS, Rockman-Greenberg C, Rauch F, et al. Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia.Bone. 2019; 121: 149-162. doi: https://doi.org/10.1016/j.bone.2018.12.011
23. Kalinchenko N.Yu., Tyulpakov A.N., Kireeva A.S. et al. The first experience of enzyme replacement therapy for hypophosphatasia in Russia. – 2016. – T. 18. – S. 1235-1240. [Kalinchenko NYu, Tyulpakov AN, Kireeva AS, et al. The first experience of the enzyme replacement therapy for hypophosphatasia in Russia. RMJ. 2016; 18: 1235-1240. (In Russ.)]
24.Shapiro JR, Lewiecki EM. Hypophosphatasia in Adults: Clinical Assessment and Treatment Considerations. J. Bone Miner. Res. 2017; 32 (10): 1977-1980. doi: https://doi.org/10.1002/jbmr.3226
When can you not do without an endocrinologist?
An endocrinologist is a doctor who deals with the diagnosis, prevention and treatment of various diseases of the endocrine system.
An endocrinologist is a doctor who deals with the diagnosis, prevention and treatment of various diseases of the endocrine system.The organs of the endocrine system are: hypothalamus, pituitary gland, thyroid and parathyroid glands, pancreas, adrenal glands, testes and ovaries. What the endocrinologist does is directly related to the hormonal regulation of the body and any violations of this function. An endocrinologist treats not only diseases, but also their consequences – restores normal metabolism, corrects hormonal balance and much more, according to endocrinologist Stepanova Victoria Rudolfovna, doctor of the Highest category.
For what symptoms should I see an endocrinologist?
Of the many symptoms, at the appearance of which it is recommended to consult an endocrinologist, the following can be distinguished: – loss or gain in weight;
- thirst, frequent urination;
- Frequent fatigue and tiredness for no reason;
- trembling of hands and feet;
- increased heart rate, increased or decreased blood pressure;
- Constant lump in the throat;
- frequent constipation;
- Deterioration of the condition of hair, skin, nails;
- menstrual irregularities, hot flashes;
- Increased male pattern hair growth in women.
What diseases are diagnosed and treated by an endocrinologist?
Diagnosis and treatment of endocrine system diseases such as:
- diabetes mellitus;
- obesity and metabolic syndrome;
- thyroid disease;
- neuroendocrine diseases;
- adrenal gland diseases;
- disorders of phosphorus-calcium metabolism (osteoporosis)
What types of endocrine diseases diagnostics are carried out in our center?
In the medical center “Diagnosis” ultrasound examinations of the thyroid gland, abdominal organs are carried out, if necessary, the measurement of the level of glucose in the blood.