Tremor is an involuntary, rhythmic oscillatory movement of at least one functional body region.
Tremor is found in every person, typically a barely visible tremor that occurs when the arms are extended and that is also observed during activities that require great precision. Pathological tremor occurs in a number of conditions, where it can appear as an isolated phenomenon, or together with other signs and symptoms. There are several practical methods of tremor diagnosis (for clinically oriented references, see Elble and Koller, 1990; Findley and Koller, 1995). While tremor amplitude and frequency are important features, they are insufficient for tremor classification. Even though time-series analysis methods have been suggested to detect, classify and diagnose tremors, none of the available methods is simple and efficient; therefore, observation by a neurologist dominates clinical practice.
For patient-oriented information about treatment of tremor and related conditions, one may look at the NIH web site http://www.ninds.nih.gov/disorders/disorder_index.htm and WE MOVE web site http://www.wemove.org
Classifications of tremors
Clinical neurological features are traditionally used to differentiate between tremors.
- Resting tremor occurs when the affected body part is not active and is supported against gravity.
- Action tremor occurs during voluntary muscle activation, and includes numerous tremor types.
- Postural tremor occurs while the affected limbs are voluntarily maintained against gravity, such as when the patient extends the arms forward in front of the body.
- Kinetic tremor occurs in both goal-directed and non goal-directed movements, as typically seen during the finger-to-nose-to-finger test in a neurological exam.
- Intention tremor is characterized by an increase in tremor amplitude as the target is approached.
- Task-specific tremors occur during isolated tasks such as writing.
Clinical assessment of tremor should include description of the location of tremor, activation condition (i.e. resting or action tremor), and tremor frequency. The presence of additional abnormal neurological signs can be an important indicator of diagnoses such as Parkinson’s disease or other neurological disorders associated with tremor.
Tremor may be classified in several other ways. Examples of tremor types in each category are given in parentheses:
- Normal or pathological condition:
- physiological tremor
- pathological tremors (with essential tremor and parkinsonian tremor being most common).
- Conditions under which tremor is most often activated:
- rest tremor (parkinsonian tremor, Holmes’ tremor, palatal tremor)
- postural tremor (physiological tremor, enhanced physiological tremor, essential tremor, orthostatic tremor, dystonic tremor, neuropathic tremor, psychogenic tremor)
- kinetic/intention tremor (cerebellar tremor, task-specific tremor, dystonic tremor, Holmes’ tremor)
- Tremor frequency:
- low frequency, less than 4 Hz (cerebellar tremor, Holmes’ tremor, palatal tremor, drug-induced tremor)
- medium frequency, 4-7 Hz (parkinsonian tremor, physiological tremor, essential tremor, task-specific tremor, dystonic tremor, neuropathic tremor, palatal tremor, drug-induced tremor, psychogenic tremor)
- high frequency, above 7 Hz (orthostatic tremor, essential tremor, physiological tremor)
Several basic tremor types and their properties are summarized in the table below.
|Tremor type||Frequency||Activation condition|
|Enhanced physiological||8-12 Hz||X|
|X - characteristic condition; x - occurs in some|
The differentiation between tremor categories above is somewhat blurred; however there have been attempts to streamline tremor nomenclature for clinical and research purposes (Deuschl et al., 1998). The amplitude of tremor does not help to distinguish tremor types, as the same tremor type (and the same pathology) may have markedly different amplitude. Clinical tremor rating scales include the Fahn-Tolosa-Marin scale (Fahn et al., 1988), which assigns 0 to 4 points for tremor amplitude under a variety of conditions and 0 – 4 points for severity in daily activities, while the Unified Parkinson’s Disease Rating Scale (Langston et al., 1992) assigns 0 – 4 points for amplitude and severity of resting and postural or kinetic tremor. Rating scale scores are on average proportional to logarithm of the displacement amplitude (Elble et al., 2006).
Physiology of some tremors
Even though each type of tremor exhibits some type of involuntary oscillatory motion, the features of the movement and of the neuronal activity in different tremor types can be quite different. These differences represent the differences in the underlying physiological mechanism and/or pathological condition. Several different mechanisms for the origin of tremor have been suggested, though for many types of tremor, the relationship between the type of tremor and these suggested mechanisms is not yet clearly established. Several types of tremor mechanisms are possible (reviewed in Deuschl et al., 2001): mechanical mechanism (every limb or limb segment has a certain resonance frequency, which depends on the load), sensory reflex mechanisms, or central oscillator mechanisms, i.e. pool of oscillatory neurons localized in a specific brain structure, or manifested as a network or loop of several different structures. Here we will consider several types of tremor, some of which are common and studied in a detail; others are less studied, but have some interesting features.
Tremor associated with Parkinson disease (PD) is one of the most widely studied and the second most common pathological tremor, with prevalence of 102-190 cases per 100,000 population in Western countries. Age at disease onset is usually after 60 and incidence increases with advancing age (Van Den Eden et al., 2003). Resting tremor is present in 80% of patients with autopsy-proven PD (Gelb et al., 1999). Asymmetrical onset of tremor is commonly observed, and tremor onset may be coincident with other parkinsonian symptoms of rigidity and slowness of movement (bradykinesia). As PD progresses the severity of tremor may diminish. Parkinsonian tremor is episodic tremor with the frequency typically in the range of 3-7 Hz. Tremor is accentuated by performing mental tasks or contralateral voluntary movements ("reinforcement maneuvers") and during ambulation. In a subset of PD patients, resting tremor may be inhibited by voluntary movement. Up to 20% of PD patients also exhibit postural or kinetic tremor (Hughes et al., 1992).
PD is characterized by the severe degeneration of dopaminergic neurons in substantia nigra pars compacta (SNc; Bernheimer et al., 1971; Pifl et al., 1991) and is associated with widespread alpha-synuclein pathology (reviewed in Golbe, 2003), with the Lewy body as the pathological hallmark (Bethlem et al., 1960). The severity of tremor is poorly correlated with the degree of dopaminergic degeneration, but even in cases where parkinsonian-like tremor is not accompanied by other PD symptoms (monosymptomatic rest tremor) dopaminergic deficit is usually present (Antonini et al., 1998). PD tremor is probably linked to the specific spatial pattern of degeneration of SNc (Paulus & Jellinger, 1991; Jellinger, 1999; reviewed in Carr, 2002).
Significant insights into tremor pathophysiology have been provided by analysis of the oscillatory activity, recorded in different parts of the nervous system. Tremor-related activity in the CNS is defined as activity in the same frequency range as and coherent with either electromyograms from tremulous muscles or tremor movements [Note: the term “tremor-related activity” is often used when two signals have oscillations within the range of tremor frequencies, without an appropriate statistical analysis of correlation.] Electrophysiological recordings in parkinsonian patients and primate models of parkinsonism have revealed tremor-related activity in different parts of the basal ganglia, such as globus pallidus (primarily in the internal segment, GPi, Hutchison et al., 1997) and subthalamic nucleus (STN, Levy et al., 2000), motor thalamus (Lenz et al., 1994) and motor cortex (Timmermann et al., 2003). Tremor-related activity has also been observed in the ipsilateral cerebellar cortex and contralateral premotor and somatosensory cortical regions (Volkmann et al., 1996).
Synchronized oscillatory activity, as revealed by LFP recordings, may be important for the function of basal ganglia and may be very widespread in PD (Hutchison et al., 2004; Boraud et al., 2005). However it is not necessarily relevant to parkinsonian tremor (e.g. reviewed in Rivlin-Etzion et al., 2006). Activity near or within the parkinsonian tremor-frequency range in LFP may correspond to the presence of involuntary movements induced by dopamine-replacement therapy – levodopa-induced dyskinesia (Silberstein et al., 2003; Alonso-Frech et al., 2006). Tremor-related activity may not be reflected in LFP recordings in tremulous patients, as the LFP is an averaged signal and, thus, depends upon the phase relationship between oscillatory units; if phase relationships are highly variable, the oscillatory signals will be averaged out (Brown and Williams, 2005).
Multiple lines of evidence support the central generation of parkinsonian tremor. Earlier studies showed that the proprioceptive feedback slightly modifies the frequency of the tremor, but does not affect its existence (Pollock & Davis, 1930; Hassler, 1970; Rack and Ross, 1986; Burne et al., 1987). The origin of the central tremor oscillator(s) remains unknown, but several hypotheses have been put forward (reviewed in Deuschl et al., 2000), including the rebound excitation thalamic oscillator hypothesis (Llinas, 1984), thalamic filter hypothesis (Pare et al., 1990), the basal ganglia pacemaker hypothesis (Plenz and Kitai, 1999; Wichmann and DeLong, 1999), and the basal ganglia – thalamo – cortical loop hypothesis (Lenz et al., 1993). Thalamic hypotheses are at odds with analysis of spike correlations in thalamic activity during parkinsonian tremor (Zirh et al., 1998). The loop hypothesis appears to be attractive, not only because anatomical and electrophysiological data point to the existence of the loop, but also because surgical lesions in different locations in the loop suppress tremor partially or completely. Cellular properties of basal ganglia and thalamic cells can support pacemaking (Surmeier et al., 2005; Llinas, 1998) and thus can contribute to the genesis of PD tremor. Recently, computational evidence has been obtained that further supports the basal ganglia – thalamo - cortical loop hypothesis and provides a possible explanation for the loop mechanism of tremor oscillations (Dovzhenok and Rubchinsky, 2012). A cerebellar origin of parkinsonian tremor has largely been ruled out based by several lines of evidence (reviewed in Deuschl et al., 2000).
Animal models of parkinsonian tremor are available (Burnes et al., 1983; DeLong, 1990; Bergman et al., 1998). In vervet monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces medium-frequency rest tremor, which resembles human parkinsonian tremor. In the other monkey species studied, MPTP treatment leads to either no tremor or high-frequency tremor different from PD tremor (Wilms et al., 1999). This is probably due to the differences in the area of the representation of the distal musculature (where tremor is most prominent) in the basal ganglia thalamocortical neuronal networks. Nevertheless, the MPTP primate model of PD is a source of valuable data on parkinsonian tremor.
Dynamics of tremor-supporting networks
Dual recordings in GPi tremor-related cells during stereotactic surgery have shown that although cells may be correlated to restricted portions of the musculature or to each other, uncorrelated oscillations within GPi are commonplace as well, even those in the close proximity to each other (Hurtado et al., 1999). During tremor episodes, limb specific regions of GPi are oscillatory overall, but the oscillation in the individual tremor-related units within that region is more sporadic. The same is true for muscular tremor. Furthermore, the synchrony between an oscillatory unit in a particular field and a particular trembling muscle within that field is intermittent (Hurtado et al., 2004, 2005). Coherence of tremor between muscles differs for different muscle pairs, with muscles from the same limb having larger coherence and muscles from different limbs (especially different sides of the body) being largely uncorrelated (Hurtado et al. 2000; Raethjen et al., 2000). The tremor in such muscles still may engage in short episodes of statistically significant coherence, but the phase difference in each episode varies (Hurtado et al., 2005). All of these findings are consistent with the view that there is a general, though not precise, topographic organization of the individual structures that comprise the tremor generating network, which exhibits spatiotemporal patterns of intermittent synchronization (Hurtado et al., 2006).
Besides oscillations and synchronous activity in the tremor frequency range, cells in STN are also oscillatory and coherent in the higher 15-30 Hz range with a very small phase lag. This synchronization is observed in tremulous patients, even when tremor is temporarily absent in limbs, but it is not observed in non-tremulous PD patients (Levy et al., 2000, 2002). 1:2 phase synchronization in cortex has also been observed in parkinsonian tremor (Tass et al., 1998).
The recognition of the dopaminergic deficit in PD led to the development of highly successful pharmacologic treatments, first with the dopamine precursor levodopa (L-dihydroxyphenylalanine), and then with a wide array of dopamine agonists, monoamine oxidase inhibitors and COMT (catechol-O-methyltransferase) inhibitors (Goetz, 2005). Monoamine oxidase and COMT inhibitors slow the break down of dopamine in the brain and, thus, can decrease the dose of levodopa needed as well as stabilize fluctuations in motor symptoms. Older agents such as amantadine and anticholinergics are considered second-line therapy. However, anticholinergic drugs are sometimes useful for tremor that is refractory to dopaminergic therapy (Nutt et al., 2005). Despite the possibility of significant improvement in motor behavior with dopaminergic therapy, the patterns of oscillatory activity in the basal ganglia are not fully reversed to the normal patterns of activity (Heimer et al., 2006).
Over time, dopaminergic therapy of PD becomes less effective as complications of on/off motor fluctuations and uncontrolled involuntary movements (dyskinesia) develop (Lang and Lozano, 1998). Medication adjustment may help, but ultimately 10-20% of PD patients with moderate to advanced disease are candidates for surgical treatment (reviewed in Tarsy et al., 2003; Walter and Vitek, 2004).
Surgical treatment involves placement of surgical lesions, deep brain stimulation (DBS) and experimental cell transplantation. There are three major targets for lesion placement: motor thalamus, GPi and STN. Thalamotomy is used to treat tremor-dominant forms of PD (Hua et al., 2003). Pallidotomy (usually lesions in posteroventral GPi) is less effective against tremor, but is effective against other PD motor symptoms (Alkhani and Lozano, 2001; Baron et al., 2000). Finally, subthalamotomy may ameliorate parkinsonian tremor, but is rarely used because of potential side effects (Alvarez et al., 2005; Gill et al., 2003).
The target for anti-tremor thalamotomy (or thalamic DBS) is the nucleus ventralis intermedius (Vim) of the thalamus, even though the nucleus ventro-oralis posterior (Vop) receives input from the basal ganglia (e.g. see discussion in Jones, 2001). In fact, Vim is an effective target for treatment of most other types of tremor, not only parkinsonian (Ohye et al., 1976; Deuschl and Bergman, 2002; Gross et al., 2006). However, there remains some debate whether the benefit of surgery arises from direct effects on the targeted nucleus or from effects on areas adjacent to the surgical target. For example, DBS in the zona incerta in close proximity to STN may be more effective than STN stimulation (probably affecting pallido-subthalamic pathways, Plaha et al., 2006).
The most common neurosurgical procedure for PD is deep brain stimulator implantation (Benabid, 2003). The same structures are targeted during electrode implantation as in ablative surgeries: STN (Abosch et al., 2003), pallidum (Volkmann and Sturm, 2003) as well as Vim thalamus (Speelman et al., 2002). After implantation, DBS electrodes deliver current pulses from a subcutaneously implanted generator. Because the tissue surrounding the electrode remains relatively intact and parameters of stimulation can be adjusted (and the electrode can be removed surgically if necessary), DBS is favored over ablative procedures.
The frequency of effective anti-parkinsonian DBS usually lies within the 100-200 Hz range and the values around 100 Hz are considered to be the threshold rate for the beneficiary effects of stimulation with the optimal frequencies being around 130 Hz (Volkmann and Sturm, 2003; Moro et al., 2002). During thalamic deep brain stimulation the amplitude of parkinsonian tremor gradually decreases with the increase of the stimulation voltage; longer duration stimulation pulses are also slightly more effective, but the frequency of stimulation does not affect the amplitude of tremor (O’Suilleabhain et al., 2003). The mechanisms of DBS are still being debated, whether blockade of action potentials or synaptic modulation, and the resultant changes in the balance of excitation/inhibition within the network or regularization of a pathological pattern of firing (Lozano et al., 2002; McIntyre et al., 2004). STN DBS reduces oscillatory activity and enforces more regular tonic spiking, correlated with the stimulation signal (Meissner et al., 2005; Garcia et al., 2005). Patients who have been treated long-term with DBS still require dopamine-replacement therapy (reviewed in Perlmutter and Mink, 2006). Recently, attempts of adaptive, “demand-controlled” DBS were introduced in theoretical studies (Rosenblum and Pikovsky, 2004; Popovych et al., 2006). The idea is that adaptive DBS will desynchronize the activity of stimulated neuronal population and thus will suppress tremor and other symptoms. It remains to be shown experimentally that desynchronization is technically achievable and can suppress tremor.
Finally, cell implantation (dopaminergic cells or stem cells form various sources) is being explored for treatment of Parkinson’s disease, but in early trials tremor was the least improved among motor symptoms. This line of treatment remains controversial and requires further investigation (reviewed in Kuan and Barker, 2005).
Essential tremor (ET) is the most common movement disorder, with prevalence of 40-390 per 100,000 (Louis, 2005). Clinically, ET presents with action tremor (postural and kinetic) with tremor frequency in the range of 4-12 Hz primarily affecting arms, but potentially also affecting neck and head, trunk and legs. ET is a slowly progressive, presumably neurodegenerative, disorder, which can sometimes become very disabling. ET is inherited as an autosomal dominant disorder in 60% of cases. The age of onset is primarily after 50 years, but there are also early-onset cases. Many mild cases are undiagnosed. At early stages, essential tremor can be similar to (enhanced) physiological tremor in clinical manifestations. Tremor is the dominant symptom of the disorder and the exact underlying pathology of the nervous system is unknown. A notable clinical feature is the tremor suppression with alcohol ingestion. There is a debate as to whether or not ET is a monosymptomatic disorder, and different variants of ET may correspond to different medical conditions (for reviews on essential tremor see Deuschl and Elble, 2000; Jankovic, 2000; Louis, 2005).
Harmaline-induced tremor in animals is generally considered to be a model for ET because it shares many properties with ET (Ahmed and Taylor, 1959; Poirier et al., 1966; reviewed in Wilms et al., 1999). Tremor-related activity in ET can be observed throughout the cortico-thalamo-cerebellar circuits (Hua et al., 1998), which is similar to tremor-related activity in basal ganglia-thalamo-cortical circuits in Parkinson’s disease. However, in some studies (e.g., Haliday et al., 2000) cortical activity synchronized with muscle electromyograms in the tremor-frequency range was not found. The number of tremor units in thalamus in ET appears to be smaller by several times than the number of tremor units in Parkinson’s disease (Brodkey et al., 2004).
Little is known about the pathology of ET. Recent post-mortem examinations revealed cerebellar Purkinje cell axonal swellings in several patients, and non-nigral Lewy body formation in a single patient (Louis, 2005). Magnetic resonance spectroscopy has revealed a reduction in cerebellar N-acetylaspartate in ET cases (Louis et al., 2002). But so far, post-mortem brain examinations in ET provided no solid evidence of apparent morphological changes. Nevertheless, essential tremor probably results from olivocerebellar pathology. Lesions in different parts of the cerebro-cerebellar-thalamic motor pathways (cerebellum, pons, thalamus) point to the cerebellar origin of essential tremor. Studies of harmaline model of ET, as well as the existence of other movement deficits in ET patients, support a cerebellar origin of essential tremor (Deuschl and Elble, 2000; Deuschl and Bergman, 2002).
Dynamics of tremor-supporting networks
Irregularity in essential tremor oscillations (similar to parkinsonian tremor) can be well approximated by second order stochastic differential equation rather than by chaotic dynamical system (Timmer et al., 2000). Oscillatory activity in the tremor frequency range in the brain is shown to be synchronized with essential tremor (measured by accelerometer or as electromyogram), and properties of this synchrony vary in space and time. Oscillations in different muscles are correlated with each other to different degrees; the more distant muscles are from each other, the smaller the correlation, and there is a poor correlation between tremor on the two sides of the body (Raethjen et al., 2000). This organization led to the hypothesis of “multiple tremor oscillators”. Similar topographical organization is observed for cortico-muscular synchronization. Moreover, the nodes of the essential tremor networks can be synchronous only for certain time-periods and be out of synchrony for other periods of time (Hellwig et al., 2003). These features of the dynamics of tremor-related activity in ET, to a degree, are reminiscent of the dynamics of parkinsonian tremor-related activity, described above.
Pharmacologic and surgical symptomatic treatments are available for ET. Since the pathophysiology of ET is unclear, different treatment targets have been explored. Beta-blockers (e.g., propranolol, atenolol, sotalol), anti-convulsant drugs (primidone, gabapentin, topiramate), and GABA agonists (alprazolam, clonazepam) are used in many patients, though their efficacy varies and side-effects can be substantial. Propanolol and primidone have been shown to reduce limb tremor and are the most commonly prescribed medication for the treatment of essential tremor. Chemodenervation with botulinum toxin injections is also effective in some patients. However, a substantial number of patients do not benefit from any available pharmacological treatment of ET (Louis, 2005; Schast et al., 2005; Zesiewicz et al., 2005).
Surgical treatment is available if essential tremor is disabling and not responsive to pharmacological treatment. The techniques of surgical treatment for essential tremor and hypotheses regarding mechanism (Hua et al., 2003; Tarsy et al., 2003) are similar to those of parkinsonian tremor, described above. Two types of surgeries are performed: ablative surgeries and implantation of deep brain stimulator. The anatomical target for the surgery is Vim nucleus of the thalamus, which is an effective target for several types of tremor (including parkinsonian tremor). However, unlike parkinsonian tremor, basal ganglia structures (subthalamic nucleus and internal pallidum) are not considered as anatomical targets in essential tremor (Speelman et al., 2002, but see also Plaha et al., 2004).
During thalamic deep brain stimulation the amplitude of essential tremor slightly decreases with the increase of the stimulation voltage (not as sharp as in parkinsonian tremor). Longer duration of stimulation pulses is also slightly more effective, but the frequency of stimulation does not affect the amplitude of tremor (O’Suilleabhain et al., 2003).
Physiological tremor and enhanced physiological tremor
Physiological tremor is present in all normal and healthy subjects and is exhibited in different conditions, such as various task execution (motion or isometric contraction), posture maintenance and even at rest. Enhanced physiological tremor is essentially the same phenomenon, but with large amplitude oscillations, occurring in the absence of a neurological disease. Physiological tremor can be enhanced by the intake of stimulants and other drugs, by withdrawal from other drugs or alcohol, during certain medical conditions (elevated thyroid hormones levels or low glucose level), and by stress and fatigue. Physiological tremor also becomes more enhanced with age. The frequency range for physiological tremor can be rather wide, from 3 to 30 Hz; enhanced physiological tremor is usually confined to 8-12 Hz range. The frequency depends on where and under what conditions tremor is observed.
There are several factors which are believed to contribute to the genesis of physiological tremor (reviewed in Elble and Koller, 1990; McAuley and Marsden, 2000; Deuschl et al., 2001). There is a mechanical component of the physiological tremor – each extremity or part of it constitutes a pendulum with a particular natural frequency, which exhibits damped oscillations for various reasons, including cardioballistic effect. This component can have a wide range of frequencies from about 4 Hz for elbow tremor up to 30 Hz for tremor in finger joints). The load on the extremity results in a decrease in the frequency. Electromyograms in physiological tremor have no clear spectral peak, primarily because there is no muscle activity at rest and this component is, strictly speaking, not neurogenic. Another component of physiological tremor results from the reflex loops in the nervous system. For this component, the load on the extremity will decrease the frequency of tremor as well as of electromyogram. Finally, there is a central component, with the frequency in 8-12 Hz range. There were several hypotheses of the origin of this component, including the involvement of inferior olive and Renshaw inhibition in the spinal cord. The relative contribution of each of these components depends on what part of the body is being considered and in what action it is involved – rest, isometric contraction, maintenance of a specific posture etc.
Dynamics of tremor-supporting networks
We are not aware of any comprehensive studies of spatiotemporal patterns of synchrony in physiological tremor, but the analysis of physiological tremor in different sides of the body showed that the coherence of physiological tremor in two body sides is low (Lauk et al., 1999).
Orthostatic tremor is a rare, unique tremor characterized by subjective sensation of loss of balance while standing, with the symptoms relieved by walking, sitting or lying down. Clinical findings are minimal, with the observation of a visible or palpable tremor in the trunk and lower extremities. Diagnosis is confirmed by electromyographic recordings from the quadriceps femoris muscle revealing a small amplitude, very high frequency (13-18 Hz) tremor while standing (Sander et al., 1988; Britton et al., 1995). Orthostatic tremor is presumed to have a central origin, even though the neural circuits responsible for its genesis are unknown. It has been proposed that the brainstem is a crucial part of these circuits (reviewed in Deuschl et al., 2001).
The distinctive feature of orthostatic tremor is its highly synchronized dynamics. Unlike many other tremors, orthostatic tremor is characterized by high values of coherence between tremor oscillations in different muscles, different limbs and even different sides of the body (Deuschl et al., 1987; Lauk et al., 1999).
Treatment of orthostatic tremor is difficult as, over-all, no pharmacological therapy produces a consistent or long-lasting effect across this patient group. The lack of response to a particular drug may be because orthostatic tremor is not a discrete disorder (reviewed in Gerschlager et al., 2004). Nonetheless, the treatment of choice has been clonazepam, as well as standard therapies for essential tremor, particularly primadone, propranolol and gabapentin. Levodopa has been reported to be effective in some patients with orthostatic tremor (Wills et al., 1999).
Cerebellar tremor is a low-frequency (3-5 Hz) intention tremor (postural tremor is also possible) due to lesions in cerebellar circuits (reviewed in Elble and Koller, 1990). Etiologies include multiple sclerosis, trauma, and hereditary cerebellar degenerations.
Dystonic tremor is a postural or kinetic tremor usually not seen at complete rest in a part of a body affected by dystonia. As basal ganglia circuits are frequently implied in pathophysiology of dystonia, dystonic tremor may have basal ganglia origins (reviewed in Deuschl et al., 2001).
Holmes’ tremor (Holmes, 1904; also known as rubral tremor, midbrain tremor, myorhythmia or Benedikt’s syndrome) is defined as a slow frequency tremor, usually below 4.5 Hz, both at rest and with intentional movements, occurring 2 weeks to 2 years following a cerebral injury such as stroke (the injury is presumed to damage basal ganglia and thalamocerebellar circuits). It is typically unilateral and affects the proximal and distal upper extremity (reviewed in Deuschl et al., 2001).
Neuropathic tremor is most commonly seen with demyelinating neuropathies of the peripheral nervous system such as Guillain-Barre syndrome, or chronic inflammatory demyelinating neuropathy. There is usually a postural or action tremor, and it can affect both upper and lower extremities. Neuropathic tremor probably occurs due to the compensatory actions of central nervous system (reviewed in Deuschl and Bergman, 2002).
Palatal tremor (previously known as palatal myoclonus) is a rhythmic vertical oscillation of soft palate which can be asymptomatic, or can cause the patient to note a clicking sound due to movement of the adjacent Eustachian tube. Symptomatic palatal tremor follows damage to the dentate-olivary pathway, with olivary hypertrophy visible on MRI imaging. Essential palatal tremor is an isolated syndrome of unknown cause, and without neuroimaging correlate (reviewed in Deuschl and Wilms, 2002).
Posttraumatic tremor is observed after certain head injuries, but the specific lesion in the brain may not be identifiable. Posttraumatic tremor may have very different features, depending on type of the trauma, and may have late onset or, on the contrary, disappear following recovery (Krauss and Jankovic, 2002).
Psychogenic tremor is another tremor for which origin is not clearly understood. In some patients it is essentially voluntary movement; in other patients it may be a different phenomenon, where exacerbation of reflexes is involved (strong muscle co-contraction is often observed in psychogenic tremor). Frequency is much less stable than that of parkinsonian or essential tremor (O'Suilleabhain and Matsumoto, 1998). The dynamics of activity of organic tremors is hard to reproduce in voluntary movement, which suggests the use of coherence measures to detect psychogenic tremor. Unlike most organic tremors, psychogenic tremor is more synchronized between different limbs and can be easily entrained by external signals (McAuley et al., 2004); however, there are patients where spatial structure of the synchrony is similar to that in organic tremors (Raethjen et al., 2004).
Task-specific tremor is observed only during execution of a very specific motor activity. Primary writing tremor is one example of task-specific tremor; it has a frequency of 5-7 Hz and is induced by writing or similar motor activity (Bain et al., 1995).
Surgical treatment (lesion or deep brain stimulation) may be effective not only against parkinsonian or essential tremor, but also against other tremors, such as dystonic tremor, posttraumatic tremor, tremor in multiple sclerosis, Holmes tremor and task-specific writing tremor. Vim thalamus is usually the anatomical target for a surgery (Speelman et al., 2002).
Tremor can be physiological or result from a known or unknown pathology, but the physiological mechanism giving rise to tremor in any condition remains unknown. The dynamics features of tremor within muscles of the limb segments and within the central nervous system (frequency of tremor and correlation within and across brain structures and muscle segments) provide clues to the nature of the pathophysiology. Most pathological tremors, except parkinsonian tremor, are poorly controlled by pharmacological treatment but several types of tremor are well-controlled by deep brain stimulation in either the thalamus, internal segment of the pallidum or subthalamic nucleus, suggesting that there is some common mechanism that involves circuit dynamics. This hypothesis, in concert with knowledge gained from physiological mapping of the brain during stereotactic neurosurgery for implantation of a deep brain stimulator and from studies of cellular and synaptic physiology of the relevant brain regions, sets the stage for modeling studies which may provide insights into the pathophysiology of tremor.
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