Primary tremor (essentialtremor, ET) is a common movement disorder. It is also known as idiopathic tremor and benign tremor. There is often a family history, so it is also known as hereditary tremor or familial tremor. 1887 Dana described the disease for the first time, over the past 100 years, despite the etiology, pathogenesis, clinical features, diagnosis and treatment of a large number of studies, it is still difficult to confirm the diagnosis, and there is no very effective way of treatment. In order to improve the understanding of this disease, a brief overview of the disease mechanism, clinical features, diagnosis, identification, treatment and basic research.
1 Pathogenesis
The pathological study of this disease has not found any abnormal changes so far, and the etiology and pathogenesis of the disease are not yet known, and it is thought that it may be related to the following aspects:
①Synchronized discharges in multiple motor units of the central or peripheral nervous system;
②The occurrence of synchronous discharges different from those in Parkinson's disease (PD), which is the main cause of the disease. 's disease (PD);
3) the result of oscillations generated within the olivocerebellar red nucleus system. Most scholars now favor a central origin of ET. A kind of 6-8 Hz tremor, characteristic of many primary tremors, appears after damage to the median ventral pallidum or lateral cerebellar system in a monkey model; clinical studies have found that stroke in the cerebellum, thalamus, and brainstem, and stereotactic surgery of the central ventral medial nucleus of the thalamus relieves tremor in humans, confirming the central mechanism. On this basis, several modes of generating postural tremor were proposed, such as the inferior olivary or the central ventral medial nucleus of the thalamus as the central oscillator, which is transmitted to the spinal cord through the projection system composed of the red nucleus, cerebellum, basal ganglia and motor cortex, producing postural tremor.
2 Clinical features
ET often has a family aggregation phenomenon, can occur at any age, the average age of onset of about 45 years of age, the prevalence of the population 410 ~ 3,920 / 100,000, the prevalence of the population over the age of 60 years of age, 1,300 ~ 5,050 / 100,000 ". Some scholars believe that the age of onset of the disease shows a bimodal pattern, with adolescence and about 50 years of age as the two peaks. There are no racial, regional, or gender differences in the prevalence of the disease.
The disease is characterized by postural tremor, and the typical ET manifestation is a single-symptom postural tremor, which is most pronounced when holding a certain position (e.g., holding chopsticks, holding a cup, etc.), and can be aggravated by movement in some patients, while others are initially accompanied by locomotor tremor, which is rarely seen at rest. It is aggravated by nervousness, emotional stress, hunger, and fatigue. All parts of the body can be affected, the affected parts are the hands, followed by the head, throat muscles, legs and chin, and seldom occurs in the trunk and the tongue; the tremor usually starts from one side of the hands, and gradually extends to the whole upper limb and the contralateral upper limb, and then upward to the head and throat muscles, and is more obvious in one side. The frequency is usually 4-12 Hz, and decreases with age, independent of the duration of the disease. It is intermittent at the beginning, gradually develops into persistent, and generally progresses slowly. Physical examination shows no other positive neurologic signs, including muscle rigidity and hypokinesia, except for tremor as the only symptom. Reactivity to alcohol is another feature of ET, about 42%-75% of ET patients drink a small amount of alcohol, the tremor is reduced or disappeared, from half an hour to a few hours, but the situation is worse after the effect of alcohol disappears.
ET is often associated with other types of movement disorders, such as PD, dystonia, myoclonus, and hereditary cerebellar ****typhosis. In addition, typical migraine has been shown to be the most common disorder associated with ET, with a 26% incidence of typical migraine reported in patients with ET.
3 The diagnosis of ET occurs throughout the life span and does not usually affect life expectancy.
3 Diagnosis
To date, there is no effective diagnostic method for ET, and the diagnosis is still limited to clinical diagnosis, which relies on the history and clinical features, and is prone to misdiagnosis or omission.
Bain and Findley et al. proposed a diagnostic criterion in 1994, which contains both inclusion and exclusion criteria.
Inclusion criteria: ①Visible and persistent postural tremor, including the hands or forearms, with or without motor tremor. The tremor may be asymmetric or asymmetric in the upper extremities, and the tremor may involve other parts of the body; (2) the tremor has persisted for at least 5 years, and symptoms may fluctuate, but cannot produce functional impairment within 5 years.
Exclusion criteria: (1) the presence of other neurological signs, but does not include cogwheel-like ankylosis and Froment's sign, which refers to the repetitive voluntary movements of the contralateral limb, inducing cogwheel-like ankylosis of the limb on the side examined; (2) known causes of physical tremor, such as hyperthyroidism; (3) the concomitant or recent use of medication that can cause tremor, or medication withdrawal symptoms; (4) tremor of known origin, such as hyperthyroidism, or the simultaneous or recent use of medication that can produce tremor, or medication withdrawal symptoms; (5) tremor of at least 5 years. withdrawal symptoms; (4) a history of trauma in the 3 months prior to the onset of tremor; (5) clinical evidence of psychogenic tremor; and (6) sudden onset of tremor.
Currently, there are many diagnostic criteria, but they vary greatly. Louis et al. in 1998 analyzed 10 sets of diagnostic criteria for ET and found that there was a 30-fold difference between them due to the fact that each criterion had different requirements for postural or/and action tremor, tremor severity, positive family history, and duration of illness. Clinical diagnosis was associated with only two factors: postural or/and action tremor and tremor severity.
Genetic diagnosis is helpful in confirming the diagnosis of ET.
4 Differential diagnosis
The disease most easily confused with ET is PD or Parkinson's syndrome. Some scholars have found that there is a high percentage of ET prevalence in the families of patients with PD; at the same time, there is a high percentage of ET-PD in ET, and often the onset of ET precedes that of PD; thus, some scholars think that ET is a kind of PD of the tonic type. However, many scholars believe that ET and PD are two different diseases. Clinical differentiation is based on the form of the tremor and neurologic signs; PD can have an action tremor, although a resting tremor is more typical. Resting tremor can be seen in various parts of the body, often asymmetrically, and is most typically characterized by a pill-rubbing motion. It is caused by flexion and extension of the elbow, forward and backward rotation of the forearm, and thumb movements at a frequency of 4-6 Hz. Typical resting tremor disappears with the onset of movement, and may become postural later in the course of the disease. Dopaminergic medication usually improves the tremor. In addition to the different forms of tremor, PD also has neurologic signs such as muscle rigidity and decreased movement.
Physiological tremor normally occurs only when a certain posture is maintained, and can be exacerbated and become a symptom in some cases and with the use of specific medications, such as anxiety, nervousness, fear, exercise, hypoglycemia, thyrotoxicosis, alcohol withdrawal, and certain medications, with a frequency of 6 to 12 Hz in the hand, and is usually characterized by the corresponding psychological or medical history, and the symptoms disappear when the triggers are removed.
In addition, this disease also needs to be identified with other diseases caused by tremor such as cerebellar lesions, demyelinating diseases, multiple sclerosis, etc., combined with the corresponding disease characteristics identification is not difficult.
5 Treatment
Drug therapy is still the main method of ET, the most commonly used drugs are. 5.1 β-adrenergic receptor blockers Clinical observation has proved that β-adrenergic receptor blockers are effective drugs for the treatment of ET, about 70% effective. Usually, 80-320 mg/d of cardiac glycosides are used, but the side effects of cardiac glycosides include slow heartbeat, fatigue, headache and shortness of breath. When choosing cardioplegia, it should be noted that chronic obstructive airway disease, atrioventricular block and asthma patients are prohibited. Metoprolol is commonly used in asthma due to its cardioselectivity. 5.2 Paracetamol An antiepileptic drug used in the treatment of ET. It has been reported to have a slightly stronger therapeutic effect than Xanax, 50-700mg per day, with an optimal dose of 250mg/d, β-blockers are ineffective in those for whom paraprazolone is effective, and vice versa, and Xanax and paraprazolone have been used in combination to achieve better efficacy: the common side-effects of paraprazolone include nausea, vomiting, dizziness, and **** dysarthria, and it is advisable to start with a small dose of paraprazolone. Therefore, it is advisable to start with a small dose of this drug, and the hepatic enzyme inducer phenobarbital can also be taken in advance.
Additionally. Phenobarbital, nimodipine, etc. are also used in ET treatment, analgesics are rarely effective. If the tremor causes severe dysfunction and does not respond to medications, stereotactic thalamotomy or deep thalamic stimulation is an option.