What Is Idiopathic Neuropathy?

Idiopathic tremor is also known as familial tremor, and about 60% of patients have a family history. No intergenerational phenomenon was found in multiple idiopathic tremor families, and gender distribution was balanced. It is generally considered to be an autosomal dominant inheritance, and it was fully revealed before 65 to 70 years of age. Incomplete manifestations and sporadic cases have also been reported. It has exactly the same clinical characteristics as those with heredity, and is generally considered to be the same disease, but the related gene abnormality has not been identified. The bimodal characteristics of the age of onset of idiopathic tremor suggest that there may be two different abnormal genes. Familial tremor is older than sporadic cases, suggesting that early-onset idiopathic tremor is more strongly affected by genetic susceptibility, and genetic susceptibility significantly affects clinical subtype characteristics.

Mao Wei

(Deputy Chief Physician)

Department of Neurology, Xuanwu Hospital, Capital Medical University

Idiopathic tremor (ET) is the most common dyskinesia. It is mainly posture, movement tremor of the hand, head and other parts of the body. Idiopathic tremor has contradictory clinical nature. On the one hand, it is a mild single-symptomatic disease; on the other hand, it is a common progressive disease with significant clinical variation. The tremor of this disease is exacerbated during concentration, nervousness, fatigue, and hunger. Most cases temporarily disappear after drinking and worsen the next day. This is also a clinical feature of idiopathic tremor. The etiology of idiopathic tremor is unclear, and it is easily confused with tremors from other diseases.

Western Medicine Name: Idiopathic tremor
English name: essential tremor, ET

Affiliated Department: Internal Medicine-Neurology
Main cause: Unknown
Contagious: Non-contagious

Idiopathic tremor disease classification

Pathogenesis and pathophysiology of idiopathic tremor

The exact cause of the disease remains unclear. Its production may be the result of the combined action of the peripheral muscle spindle afferent and the central autonomic oscillator. The ventro-intermediate nucleus (VIM) is the nucleus that accepts proprioceptive afferents, and the rhythmic burst discharge activity of its neurons may play a key role, which is confirmed by both neurophysiological recording and stereotactic surgery . PET studies with CO2 labeled with oxygen (15 [O]) found that the bilateral cerebellum and inferior olive nucleus were selectively hypermetabolic. Functional magnetic resonance imaging (FMRI) showed increased motor activity in the contralateral cortex of the affected limb, pale globules, and thalamus, and bilateral dentate nucleus, cerebellar hemisphere, and red nucleus activity increased. These suggest that the occurrence of tremor is the result of cerebellar-olivine nucleus oscillations in the thalamus and motor cortex to spinal cord pathways. Because there is no specific change in pathological anatomy, the position of the "pacer" of the central nervous system with abnormal vibrations is unclear, so it is speculated that the central oscillator is enhanced or suppressed by peripheral reflexes to regulate the occurrence of tremor and the amplitude of tremor.

Clinical manifestations of idiopathic tremor

Idiopathic tremor multiple groups

1. Family history Idiopathic tremor is also known as familial tremor. About 60% of patients have a family history, showing autosomal dominant genetic characteristics. Researchers' reports on family history vary from 17.4% to 100%. The reason for this huge difference is the different diagnostic criteria for idiopathic tremor. The correct evaluation of the family history of idiopathic tremor depends on the consultation of tremor symptoms and clinical examination.

2. The typical incidence of idiopathic tremor can be found in children, adolescents, middle-aged and elderly people, and the incidence rate in the general population is 0.3% to 1.7%, and it increases with age. Incidence increased to 5.5% in people over 40 years of age, and 10.2% in people over 65 years of age. There is no significant difference in incidence between men and women, and a 0.5: 0.71 incidence rate has been reported for women and men in Sweden and Finland. Idiopathic tremor may be more common in left-handed people.

3. Age of onset Idiopathic tremor can start at any age, and there are two views on the peak age of onset. One considers that the distribution of onset age is bimodal, that is, between 20-30 years old and 50-60 years Another view of these two age groups is that idiopathic tremor rarely occurs in adolescents, and the number of people with onset increases with age, with an average onset age of 37 to 47 years.

4. The age of onset of tremor has nothing to do with the development of the disease. Most scholars believe that the disease progresses slowly and never remissions. Labor loss due to tremors begins 10 to 20 years after the onset of illness, and the incidence increases with the duration and age of the disease.

Idiopathic tremor disease symptoms

The only symptom of idiopathic tremor is tremor, occasionally reported with intonation and slight gait abnormalities. Patients usually start with the upper limbs, which mainly affect the upper limbs. They can also affect the head, legs, torso, sound, and facial muscles. Presented as postural tremor, which can contain sports, intentional or stationary tremor at the same time. Tremors can worsen in purpose-directed movements. The frequency of tremor is 4 ~ 8Hz. The frequency of onset is 8-12 Hz. With the increase of disease duration and age, the frequency gradually decreases and the amplitude gradually increases.

Patients often feel vibrations in the body for the first few months, and then tremor during short-term activities when excited or tired later, and then tremor persists. You can control yourself in a short time, and the impact on the activity is not obvious. At this stage, postural tremor is reflective and appears quickly, lasting only a few seconds. With the increase of tremor amplitude, it is often difficult to control and even affect work. Even severe tremors often fluctuate and sometimes disappear temporarily when they maintain their posture. The tremor amplitude and frequency often change with different actions and maintaining different postures. At this time, tremor can still be suppressed by itself, but it is more difficult and shorter.

Idiopathic tremor is generally considered to be symmetrical onset of bilateral upper limbs, but also unilateral upper limbs. Once affected by the upper limbs, it often progresses up to the head. surface. Tongue, jaw. Cumulative torso and bilateral lower limbs are rare, appear only in the late stages of the disease, and are less severe than upper limbs.

Typical symptoms are rhythmic abduction and flexion-extension tremor of the hand. Pronation and supination-like tremor (similar to Parkinson's disease) are rare. Written characters may be distorted, but they do not appear to be too small. Another commonly affected area is the craniocervical muscle group, which can be accumulated in the head, tongue, or vocal muscles. It is manifested by severe posture tremor and head tremor in the patient's hand, including vertical "nodding" motion and horizontal Shake your head. Soft palate and tongue tremor can make speech difficult.

The tremor will affect the activity 10 to 20 years after the onset, and the severity increases with age, so that the ability to complete surprise activities is impaired, reaching a peak in the sixth 10 years after the onset. 86% of patients are between 60 and 70 years of age, and their growth can affect social activities and living abilities, including writing, drinking, diet, dressing, speech and manipulation. The greater the growth rate, the greater the impact on activity capacity. There was no difference in the effects of tremor on gender. Many factors can affect tremor. Hunger, fatigue, emotional agitation, and temperature (high fever, hot bath), etc., can increase tremor. As with most involuntary movements, idiopathic tremor resolves during sleep, and there have been individual reports that tremor persists during sleepiness.

Idiopathic tremor is characteristic in response to ethanol (alcohol). Many patients can reduce tremor even with a small amount of ethanol. In 42% ~ 75% of patients, the tremor was reduced after drinking, but it was only temporary. It usually lasted for 2 ~ 4 hours, and the tremor worsened on the second day. Ethanol has rarely been reported to have similar effects on other types of tremors, and ethanol works through the center.

It has been reported that idiopathic tremor can be accompanied by other movement disorders. In patients with idiopathic tremor, the incidence of Parkinson's disease is much higher than in normal controls. Even in patients with idiopathic tremor older than 60 years, the risk of Parkinson's disease is 24% of that in a random population of the same age group. Times. Postural tremor is common in many dyskinesias, including Parkinson's disease, and even the only early symptoms. Lack of strict diagnostic criteria can lead to misdiagnosis of idiopathic tremor.

6.6% ~ 47% of patients with idiopathic tremor have dystonia. Postural tremor is also common in dystonia, especially writing spasticity, with 7% ~ 23% of dystonia associated with idiopathic tremor. Spastic torticollis is often accompanied by head and trunk tremors.

Idiopathic tremor may have atypical tremor manifestations, including hand dyskinesia, combined resting and postural tremor, primary writing tremor, limited vocal tremor, jaw tremor, limited tongue tremor, and upright Sexual tremor.

Tremors that have been confined to one part of the body during the course of the disease cannot be considered as idiopathic tremors. Such as tongue tremor, mandibular tremor, vocal tremor, primary upright tremor, and occupational tremor task-specific tremor, these localized tremor can be considered as idiopathic tremor when the typical characteristic tremor appears in the course of the disease. Variant.

Idiopathic tremor diagnosis and differential diagnosis

Idiopathic tremor diagnosis

Idiopathic tremor should be considered when middle-aged and elderly people have obvious persistent postural tremor accompanied by exercise tremor.

(A) the diagnostic criteria of idiopathic tremor

1. Visible, continuous postural tremor or tremor in other parts of the body that are visible to the naked eye with both hands or both forearms. Bilateral postural tremor can be asymmetric, and generally continuous tremor is large and fluctuating. Tremors can affect life and work.

2. The course of disease must be more than 3 years.

3. Clear diagnosis must exclude the following conditions

(1) There are other abnormal signs of nervous system except tremor.

(2) Application of drugs or drug withdrawal conditions and diseases that can cause tremor.

(3) Within 3 months before the occurrence of tremor, there were clear neurological traumas, including tremors in which the head trauma was consistent with the distribution of peripheral nerve trauma.

(4) There are obvious psychological factors that can cause tremor.

(5) Sudden occurrence of tremor or rapid deterioration.

(B) may be the proposed diagnostic criteria for idiopathic tremor

1. The same tremor characteristics as the "diagnostic criteria", but tremor is not in the predominant location, including posture tremor in the head and legs.

2. The course of disease is more than 3 years.

(1) The same exclusion criteria as the "Confirmed Diagnosis Criteria".

(2) Primary orthostatic tremor (14-18Hz tremor in both lower limbs when standing).

(3) Localized vocal tremor (speech idiopathic tremor, which alone involves vocalization, cannot be separated from speech disorders caused by dystonia of the pharyngeopharynx and other vocal organs)

(4) Localized postural tremor includes task-specific tremor including occupational tremor and primary writing tremor.

(5) Confined tongue tremor or jaw tremor.

(6) The abnormal posture of the head may indicate dystonia of the head.

Idiopathic tremor is often misdiagnosed and is generally considered to be early or enhanced physiological tremor of Parkinson's disease. Inconsistent diagnostic criteria are the main reason. A diagnosis of idiopathic tremor must exclude other neurological disorders. At present, patients with tremor that meet the diagnostic criteria for idiopathic tremor can be seen clinically. But accompanied by Parkinson's syndrome (disease), dystonia, muscle cramps, restless leg syndrome and other extrapyramidal diseases or peripheral neuropathy. The diagnostic method at this time can draw on the overlay diagnostic methods commonly used in degenerative diseases, such as Parkinson's overlay syndrome. Idiopathic tremor is superimposed (ET PLUS), such as idiopathic tremor and Parkinson's disease.

(Four) auxiliary inspection

(1) CT, MRI, positron emission tomography (PET) or single photon emission tomography (SPECT), which is meaningful for differential diagnosis.

(2) The electromyogram (EMG) can record the continuous release activity of the activator-antagonist muscle synchronization at 4-8 Hz, and about 10% of patients show alternating contraction of agonist-antagonist muscle. Single motion unit analysis showed that the electrical impulses were collective or synchronized. The newly recruited motor units in the recruitment phase during the tremor had an abnormally high instantaneous 20-50 Hz discharge frequency.

(3) Genetic analysis is of great significance for the diagnosis of some hereditary dystonia diseases.

Differential diagnosis of idiopathic tremor

The differential diagnosis of idiopathic tremor and Parkinson's disease is important. Parkinson's disease is more common in the elderly. This period is also the multiple age of idiopathic tremor, so many idiopathic tremors are misdiagnosed as Parkinson's disease. Although typical Parkinson's disease is characterized by resting tremor, myotonia, and bradykinesia, it is often lacking characteristic manifestations early in the course of the disease, especially tremor at the time of onset, especially postural tremor (this is It is also very common), which can easily lead to misdiagnosis.

Parkinson's disease progresses to tremor of the head, lips, tongue, and jaw rarely. Patients with long-term hand tremor may occasionally develop typical Parkinson's disease, but it is unclear whether it was Parkinson's disease or idiopathic tremor and later developed Parkinson's disease. Neuroelectrophysiology is helpful for identification. The tremor frequency of Parkinson's disease is mostly 6Hz when the main position is tremor. The postural tremor frequency of idiopathic tremor is 4 ~ 8Hz. Most are 6 to 6.5 Hz, so it is difficult to distinguish between idiopathic tremor and postural tremor-based Parkinson's disease based on frequency analysis alone. If Parkinson's disease is dominated by resting tremor, it is not difficult to identify. When the patient relaxes in a resting position, the amplitude of the tremor is much larger than when maintaining a certain posture, but the frequency is low. The resting tremor component of idiopathic tremor The frequency of tremor is almost the same (about 0.5Hz smaller), but the amplitude of tremor is much smaller. Although frequency analysis alone is not sufficient for identification, it is still helpful to distinguish between the two through changes in rest and posture. PET scans found that 18F-dopa was normally taken up by the putamen in patients with idiopathic tremor, the dopamine D2 receptor function was normal and the dopamine transporter function was normal in the basal ganglia, and 18F-dopa was reduced by the putamen in the Parkinson's disease. D2 receptor function is up-regulated and dopamine transporter function is weakened.

Both enhanced physiological tremor and idiopathic tremor appear as posture tremor and exercise tremor. Increased physiological tremor can often find the cause of enhanced tremor, such as hyperthyroidism, lithium or valproic acid poisoning, ethanol (alcohol) withdrawal, etc. However, it is difficult to distinguish between enhanced physiological tremor and suspected idiopathic tremor with peripheral neuropathy. These peripheral neuropathies can be hereditary neuropathies such as peroneal muscular atrophy (Charcot-Marie-Tooth disease), hypertrophic interstitial polyneuritis (hypertrophic interstitial polyneuritis), or the recovery period of Guillain-Barre syndrome. An inertial loading test can help identify if there are movement and postural tremors at 6-10 Hz in both hands, supporting the diagnosis of idiopathic tremor. Idiopathic tremor is not difficult to distinguish from primary orthostatic tremor. Leg tremor of idiopathic tremor is also present when walking and standing. The frequency of leg tremor is 7.5-10Hz; Orthostatic tremor 14-16Hz tremor only occurs when standing, disappears while sitting and walking. ^[1]

Treatment of Idiopathic Tremor

Most patients with idiopathic tremor have only mild tremor, and only 0.5% to 11.1% of patients need treatment. Of these, less than 50% of patients use drugs to control symptoms well, and the remaining patients are not sensitive to drugs and the treatment effect is not good. Need botulinum toxin injection or stereotactic therapy.

Idiopathic tremor medication

l. Ethanol (ethanol) It was found early that drinking alcohol can significantly reduce the tremor in most patients temporarily. Even a small dose of ethanol (alcohol) will also have a dramatic effect, but tremor reappears after 2-4 hours, and the amplitude is greater. Clinical findings have grown over time and more ethanol (alcohol) is needed to suppress tremor. The long-term treatment of idiopathic tremor with ethanol (alcohol) can lead to alcoholism. Therefore, ethanol (alcohol) cannot be used as a long-term treatment, and alcohol withdrawal can also cause tremor. But occasionally you can use ethanol (alcohol) to control symptoms. The mechanism of action of ethanol (alcohol) is unclear. May act on the cerebellum.

2. Adrenal -blocker propranolol has a positive effect on idiopathic tremor. No other selective or non-selective adrenal beta-blocker has been found to be more effective than propranolol. Most reports confirm that propranolol can reduce the postural tremor amplitude without reducing the frequency. The effects of tremors in other parts of the body are not ideal, or even completely ineffective. The effect of treatment is not related to blood concentration, and the reason is unclear.

Adrenal beta-blockers block endogenous catecholamines acting on the center and periphery. Studies have shown that propranolol has the highest fat-soluble properties and acts on the central system through the blood-brain barrier, so it has the best effect. According to the size of fat-soluble adrenal beta-blockers, propranolol, metoprolol, sotalol, and atenolol are in order, but for idiopathic tremor The efficacy was propranolol, sotalol, atenolol, and metoprolol in that order. Therefore, adrenal beta receptors function not only through central mechanisms, but also peripherally. Sites of peripheral catecholamine receptors exist in the inner and outer spindle muscles. The 2-receptors acting on the external spindle muscles work by shortening the twitch cycle and strengthening postural tremor. 2-receptor antagonists block this effect to reduce tremor.

Propranolol has a good effect on idiopathic tremor, but there are still a considerable number of patients who do not respond well to it. Symptoms can be reduced by 50% to 70% from 50% to 70%. The therapeutic effect of propranolol is related to the dose. Although individual patients have been effective at 80mg / d, for most foreign patients, 120mg / d The dose is still inadequate, and generally requires 240 to 320 mg per day, but a larger dose does not cause a corresponding increase in side effects. It is recommended that propranolol be taken 3 times a day starting from a small dose, and it will take effect after a few days. It will increase by 10 to 20 mg every 2 days, but long-term medication will lead to tolerance. After long-term use, withdrawal should be slow (more than 1 week) to prevent withdrawal reactions such as tachycardia, sweating, tremor, and general discomfort.

Relative contraindications for propranolol treatment are cardiac insufficiency, second- or third-degree atrioventricular block, asthma or other bronchospasm disease, and insulin-dependent diabetes. Most of the side effects are the corresponding adrenal beta-blocking effect and reduced pulse rate, but the heart rate can be tolerated more than 60 times. Other rare side effects include fatigue, weight gain, nausea, diarrhea, rash, impotence, and changes in mental state (such as depression). Most of propranolol side effects can be tolerated after a period of treatment. If it is an asthma patient, 2-receptor blockers and propranolol are not suitable. Selective 1-receptor blockers such as atenolol and metoprolol can be applied.

In some patients with idiopathic tremor, tremor only occurs in predictable special occasions. Taking propranolol intermittently can control symptoms well. Taking medicine 1 hour before the onset can effectively prevent the occurrence of tremor.

3. If idiopathic patients have chronic obstructive airway disease, cardiac insufficiency, or peripheral vascular disease at the same time, propranolol is contraindicated and primidone is the first choice. For large-scale tremors, pumipone is more effective than propranolol, and can even reduce tremors to asymptomatic amplitude ranges.

Pamilidone is a commonly used antiepileptic drug, which is completely absorbed in the upper digestive tract and reaches a peak serum concentration within 3 to 5 hours. Pumipone is converted into two active metabolites in the body, one is unbound phenylethylene malonamide. About 50%, the half-life is 24-48 hours, and about half of the product phenobarbital is combined, the half-life is 120 hours. During the chronic administration of phenobarbital, the serum steady-state concentration was reached after 3 weeks. The anti-tremor effect of perimetone is unknown. Phenobarbital has a GABA-like tincture, while polimetone has similar pharmacological mechanisms as carbamazepine and phenytoin, both acting on nerve cell membranes and altering ion influx.

Pmiridone can be used to treat idiopathic tremor at 125 mg twice a week, and up to 250 mg three times a week. This dose significantly reduces tremor in patients who have never been treated or who have used propranolol. 1/5 of patients treated with polimetone may have acute toxicity, such as dizziness, nausea, and vomiting, even with very small doses. So the starting dose is 62.5mg once daily. The dosage should be increased slowly, increasing by 62.5mg every 2 days, until the therapeutic effect is good without side effects. The treatment of tremorone by polimizone has more side effects than the treatment of epilepsy. The acute reaction of the first dose and the side effects of large doses often lead to treatment interruption. Nausea, vomiting, and ataxia are delayed metabolism induced by liver enzymes, but its metabolite phenylethylene malonamide has no side effects, and phenobarbital has few side effects. If intolerable side effects occur, phenobarbital can be substituted, but only with moderate effects.

If the effect of a single medication is not satisfactory, you can try combined propranolol and pumipone.

4. Other drugs In a small sample open study, 0.15 to 0.45 mg / d clonidine is effective. In addition, low-dose clozapine (18-75 mg / d) is effective for most patients. Clonazepam is usually ineffective for idiopathic tremor, but can be made small with idiopathic tremor mainly composed of exercise components. Carbonic anhydrase inhibitor (methozolamide) is highly effective against head and vocal tremor, but it has also been reported to be completely ineffective

Idiopathic tremor non-drug therapy

1. botulinum toxin-A injection A type of botulinum toxin-A blocks the release of acetylcholine from peripheral nerve endings, causing a certain degree of muscle weakness, which is effective in 67% of patients. The longest effective period is 10.5 weeks, and weakness is the most common side effect.

2. Stereotactic surgery Stereotactic thalamus surgery can significantly reduce idiopathic tremor, but few people need brain surgery to improve symptoms. The target of thalamic surgery is the thalamic ventral nucleus and its lower structures, including zone incerta and subthalamic nucleus. Surgery includes destructive surgery and electrical stimulation.

Destroyer of thalamus has achieved 80% of patients with moderate or higher curative effect after surgery, and some patients have unsatisfactory treatment for the first time. Reoperation after 2 months can still significantly improve. Destroyer of thalamic ventral nucleus is suitable for unilateral limb tremor, and 4% ~ 20% relapse within 1 year. Surgical complications include intracranial hemorrhage, meningitis, paresthesia, and extrapyramidal damage. Surgical mortality was only 0.5%. Short-term intellectual impairment, dysarthria, dysphagia, and paresis may occur after surgery. Serious complications can occur in more than 25% of bilateral surgeries. Such as speech disorders, mental changes, and involuntary movements are permanent, so we do not recommend bilateral thalamus nucleus destruction.

The therapeutic effect of high-frequency electrical stimulation of thalamic ventral nucleus is superior to or equivalent to that of mutilation. Long-term high-frequency stimulation electrodes were implanted in the thalamic ventral nucleus. The stimulator was turned on during the day and turned off at night. The effect was significant and the side effects were mild. The biggest danger of the operation is intracranial hemorrhage. 32% of side effects have mild discomfort, such as eating, leg dystonia, or balance disorders, but they can be tolerated, and all discomfort disappears when the stimulator is closed. No serious complications were found on the bilateral implant electrodes, which is especially suitable for patients with clinical manifestations of bilateral limb tremor.

The thalamic ventral nuclear electrical stimulation has the advantages of reversibility, less disruption, easy adaptation, self-regulation, and control of bilateral limb symptoms. Disadvantages are frequent adjustments, potential infection risks, and susceptibility to external magnetic interference.

Idiopathic tremor disease prognosis

The age of idiopathic tremor has nothing to do with prognosis, and the severity of tremor has nothing to do with mortality. Although idiopathic tremor is often referred to as "benign" and is stable for a long time or for life, some patients with severe tremor can cause difficulty in movement, reduce social interaction activities, and eventually lose labor and make life difficult. This condition usually occurs more than ten years after the onset of illness, and the incidence increases with age. As many as 15% of patients may retire early due to incapacity.