Tremor: causes, symptoms, diagnosis, treatment

Tremor is an involuntary vibration of any part of the body caused by alternating or synchronous contractions of reciprocally innervated muscles.

Diagnosis of the underlying disease of tremor is often a very complex task, the solution of which requires, first of all, a correct syndromic description of tremor. In connection with the above, great importance is attached to the principles of clinical description of tremor.

• The most important principle is a clear distinction between three types of tremor: rest tremor, postural tremor and intention tremor. If the same patient has not only rest tremor, but also postural or intention tremor, then all types of tremor are described and recorded as separate independent types, necessarily emphasizing the relative severity of each of them. For example, a patient may have a severe rest tremor, a less pronounced postural tremor and an even less pronounced intention tremor. Such a picture is typical for severe tremor forms of Parkinsonism. These same components of tremor outside Parkinsonism usually have different relationships: either postural tremor predominates (which is typical for severe essential tremor) or intention tremor (in case of cerebellar lesions).
• Other important principles for describing tremor are:
  • Localization (arms, head, facial muscles, lower jaw, tongue, lips, cheeks, vocal cords, legs, torso), distribution features (by hemitype, generalized, etc.), as well as other topographic features (for example, tremor of only the thumb or abdominal wall muscles, tremor of the eyeballs or orthostatic tremor, distal or proximal accentuation of tremor, symmetry/asymmetry).
  • Motor pattern of tremors (flexion-extension; pronation-supination; “rolling pills”, “yes-yes”, “no-no”; flapping).
  • Amplitude-frequency characteristics, severity of tremors, features of its course (variants of debut and subsequent dynamics).
  • Syndromic environment of tremor, that is, a description of those neurological symptoms against which tremors appear.

Compliance with the above principles of describing tremor syndrome is a necessary prerequisite for successful differential and nosological diagnosis of tremor.

What causes tremors?

• Resting tremor (3.5-6 Hz).
  • Parkinson's disease.
  • Secondary (symptomatic) parkinsonism.
  • “Parkinsonism plus” syndromes and other hereditary degenerative diseases accompanied by Parkinsonism syndrome (Wilson-Konovalov disease, Hallervorden-Spatz disease, etc.).
• Postural tremor (6-12 Hz).
  • Physiological tremor.
  • Increased (accentuated) physiological tremor (during stress, endocrine diseases, intoxication).
  • Benign essential tremor (4-12 Hz): autosomal dominant, sporadic, in combination with some diseases of the central nervous system (Parkinson's disease, dystonia) and peripheral nervous system (polyneuropathy, reflex sympathetic dystrophy).
  • In case of organic pathology of the brain (toxic, tumor and other lesions of the cerebellum, Wilson-Konovalov disease, neurosyphilis).
• Intention tremor (3-6 Hz) is caused by damage to the brainstem, cerebellum and their connections (multiple sclerosis, degeneration and atrophy in the brainstem and cerebellum, Wilson-Konovalov disease, vascular diseases, tumors, intoxication, TBI, etc.).
• Rubral tremor.
• Psychogenic tremor.

Neurochemical changes in tremor

Examination of the brains of deceased patients with essential tremor has not revealed any specific pathological changes or a specific neurochemical defect. Although lesions of the cerebellar efferents or afferents can cause tremor, whether any specific neurochemical defect underlies it remains unclear. Neuroimaging studies help to identify the neural circuits involved in the pathogenesis of tremor.

Types of tremor

Resting tremor

Resting tremor usually has a frequency of 3.5-6 Hz. Low-frequency (usually 4-5 Hz) resting tremor is a typical manifestation of Parkinson's disease, as well as many other diseases of the nervous system accompanied by parkinsonism syndrome, so it is often called parkinsonian tremor. Secondary (symptomatic) parkinsonism (vascular, postencephalitic, drug-induced, toxic, post-traumatic, etc.) also usually manifests itself with tremor (although it is less typical for vascular forms of parkinsonism), which has the same characteristics as in Parkinson's disease (low-frequency resting tremor with a characteristic distribution, course and tendency to generalization).

Postural tremor

Postural tremor occurs in a limb when it is held in a certain position. This tremor has a frequency of 6-12 Hz. Postural tremor includes physiological tremor (asymptomatic tremor), increased (accentuated) physiological tremor that occurs during emotional stress or other "hyperadrenergic" conditions (thyrotoxicosis, pheochromocytoma, administration of caffeine, norepinephrine and other drugs), essential tremor, as well as tremor in some organic diseases of the brain (severe cerebellar lesions, Wilson-Konovalov disease, neurosyphilis).

Intention tremor

Intention tremor has a characteristic motor pattern, its frequency is 3-5 Hz. Intention tremor is typical for damage to the brainstem, cerebellum and its connections (multiple sclerosis, degeneration and atrophy of the cerebellum and brainstem, Wilson-Konovalov disease, as well as vascular, tumor and toxic lesions of this area of the brain). Their diagnosis is carried out by characteristic accompanying neurological symptoms indicating the involvement of gray and white matter in the brainstem and cerebellum, often with a typical picture on CT or MRI.

It should be remembered that cerebellar variants of tremor include not only intentional tremor, but also such phenomena as titubation, which manifests itself in rhythmic oscillations of the head and sometimes the torso (especially noticeable when the patient is standing), and postural tremor of the proximal parts of the limbs (thighs or thighs).

Rubral tremor

Rubral tremor (more correctly called midbrain tremor) is characterized by a combination of resting tremor (3-5 Hz), even more pronounced postural tremor and maximally pronounced intention tremor (intention tremor → postural tremor → resting tremor). It appears with damage to the midbrain due to stroke, craniocerebral trauma or, less often, with a tumor or demyelinating (multiple sclerosis) process in the legs of the brain. This tremor appears in the limbs opposite the side of the midbrain lesion.

Psychogenic tremor

Psychogenic tremor is one of the variants of psychogenic movement disorders. Clinical criteria of psychogenic tremor include sudden (usually emotional) onset, static or wave-like (but not progressive) course, presence of spontaneous remissions or remissions associated with psychotherapy, "complex" nature of tremor (all main types of tremor can be equally represented), presence of clinical dissociations (selective preservation of some functions of the limb in the presence of gross tremor in it), placebo effectiveness, as well as some additional signs (including complaints, anamnesis and results of neurological examination) confirming the psychogenic nature of the disorder.

Physiological tremor

Physiological tremor is present in the norm, but manifests itself in such small movements that it becomes noticeable only under certain conditions. Usually it is postural and intentional tremor, low-amplitude and fast (8-13 per 1 second), revealed when stretching the arms. Physiological tremor increases in amplitude with anxiety, stress, fatigue, metabolic disorders (for example, hyperadrenergic states during alcohol or drug withdrawal or thyrotoxicosis), in response to the use of certain drugs (for example, caffeine, other phosphodiesterase inhibitors, beta-adrenergic agonists, glucocorticoids). Alcohol and other sedatives usually suppress tremor.

Unless there are serious complaints, no treatment is required. Physiologic tremor, which increases with alcohol withdrawal or thyrotoxicosis, responds to treatment of these conditions. Benzodiazepines orally 3-4 times daily (eg, diazepam 2-10 mg, lorazepam 1-2 mg, oxazepam 10-30 mg) are helpful for tremor associated with chronic anxiety, but their long-term use should be avoided. Propranolol 20-80 mg orally 4 times daily (as well as other beta-blockers) is often effective for tremor associated with medications or acute anxiety (eg, stage fright). If beta-blockers are ineffective or not tolerated, primidone 50-250 mg orally 3 times daily may be tried. Small doses of alcohol are sometimes effective.

Other types of tremors

The so-called dystonic tremor (trembling spasmodic torticollis, trembling writer's cramp), "rabbit" syndrome (neuroleptic tremor of the lower jaw and lips) are mentioned in the literature as independent phenomena. Phenomenologically, such rhythmic phenomena as asterixis (flapping, negative myoclonus), myorhythmia, segmental myoclonus resemble tremor, however, according to the mechanism of formation, they do not belong to tremor.

Special forms of tremor (orthostatic tremor, “smile tremor”, vocal tremor, chin tremor - geniospasm) are considered variants of essential tremor.

The most common type of postural and kinetic tremor is enhanced physiological tremor, which usually has low amplitude and high frequency (12 cycles/s). Physiological tremor increases after physical exertion, with thyrotoxicosis, and with the use of various medications such as caffeine, adrenergic agents, lithium, and valproic acid.

Essential tremor

The next common type of tremor is the so-called essential or familial tremor, which is usually slower than enhanced physiological tremor. Essential tremor can involve the limbs, as well as the head, tongue, lips, and vocal cords. Tremor intensifies under stress and in severe cases can lead to disability of the patient. Patients with this type of tremor often have close relatives suffering from the same disease. However, the localization and severity of tremor within a single family vary significantly. Limbs can be involved asymmetrically, but strictly unilateral tremor usually indicates another disease. Tremor often decreases after drinking alcohol, but is intensified by caffeine, stress, or concomitant thyrotoxicosis (like enhanced physiological tremor). Tremor can be asynchronous in different limbs - in contrast to synchronous resting tremor in Parkinson's disease. In this regard, a patient who is unable to hold a cup of liquid with one hand without spilling it due to tremors copes with this task much better by holding the cup with both hands - the asynchronous movements of the hands partially dampen each other's vibrations.

Benign essential tremor currently includes not only autosomal dominant and sporadic variants of essential tremor, but also its combinations with other diseases of the central and peripheral nervous system, including dystonia, Parkinson's disease, peripheral neuropathies (CIDP, hereditary sensorimotor neuropathy types I and II, GBS, uremic, alcoholic and other polyneuropathies).

There are several options for diagnostic criteria for essential tremor, below is one of the most commonly used.

Diagnostic criteria for essential tremor (Rautakoppi et al., 1984).

1. Frequent (at least several times a week) or persistent tremors of the limbs and/or head.
2. Postural or kinetic nature of tremor (possibly with or without an intentional component).
3. Absence of other neurological diseases that can cause tremor.
4. No history of treatment with any drugs that may cause tremor.
5. A family history of similar tremors in other family members (confirms the diagnosis).

Tremor may occur in other extrapyramidal diseases, such as myoclonic dystonia, characterized by rapid muscle twitching. Orthostatic tremor and isolated postural tremor are distinguished as separate variants. Currently, an active search is underway for a genetic defect in essential tremor. To date, it has been possible to map the gene only in individual familial cases, but its product has not yet been identified. It is possible that the disease is associated with multiple genes. Different families often differ in their reaction to alcohol, the presence of concomitant extrapyramidal syndromes (myoclonus, dystonia, parkinsonism). After identifying the genetic defect in different families, it will be possible to determine which clinical nuances are genetically determined and which simply reflect the phenotypic variability of the disease.

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Cerebellar tremor

In cerebellar lesions, tremor usually also has a kinetic and postural character. Low-frequency oscillations of the limb occur as a result of instability of its proximal section. At the same time, tremor passes if the limb is stabilized. Differentiation of cerebellar and essential types of tremor usually does not cause difficulties. Cerebellar tremor intensifies as the limb approaches the target, whereas with essential tremor the amplitude of hyperkinesis remains approximately the same throughout the execution of the entire targeted movement. In cerebellar lesions, in addition to tremor, there is also a pronounced impairment of fine motor coordination, whereas with essential tremor, motor coordination is usually not affected.

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Tremor treatment

Several medications are used in the treatment of essential tremor - beta-adrenergic receptor antagonists, benzodiazepines and primidone. The most effective are beta-adrenergic blockers, which reduce the amplitude of tremor and often cause significant clinical improvement. Low doses of benzodiazepines (especially clonazepam) can also reduce the severity of essential tremor. They are used as monotherapy or in combination with beta-adrenergic blockers. However, since tolerance to the action of these drugs can develop over time, they are recommended not to be used regularly, but as needed - for example, before a public event or during a period of particular stress. Alcohol can be used to reduce tremor, but the risk of developing alcoholism limits its use. However, drinking an alcoholic beverage before a meal can allow you to eat and drink more calmly. Finally, to reduce essential tremor, small doses of primidone (25-250 mg/day) are used as monotherapy or in combination with beta-blockers.

Pharmacotherapy for cerebellar tremor is usually ineffective. However, there are reports of successful treatment with clonazepam and primidone. Stereotactic thalamotomy or thalamic microstimulation may be an effective approach to the treatment of severe cerebellar tremor.