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Chapter 22 Physiologic and enhanced physiologic tremor
Movement Disorders Handbook of Clinical Neurophysiology, Vol. I M. Hallett (Ed.) © 2003 Elsevier B.V. All rights reserved
357 CHAPTER 22
Physiologic and enhanced physiologic tremor Rodger J. Elble* Department of Neurology, Southern Illinois University School of Medicine, P.O. Box 19643, Springfield, 1L 62794-9643, USA
Healthy people exhibit rhythmic oscillations in body position and muscle contraction, and these oscillations are called physiologic tremor. The mechanisms of physiologic tremor are reviewed in this chapter.
22.1. Passive mechanical oscillation The friction and viscous damping in most joints are not sufficient to prevent passive mechanical oscillation in response to a perturbation. Skeletal muscle behaves as a low-pass filter in response to motor-unit excitation, and this filtering effect limits the fluctuations in muscle force caused by irregularities in motor unit firing (Stein and Oguztoreli, 1976). However, these irregularities are not filtered completely, and they continuously perturb associated joints into oscillation. Muscle-spindle and tendonorgan reflex loops lack the sensitivity to attenuate these small oscillations, and the underdamped mechanical properties of most joints are conducive to oscillation (Hagbarth and Young, 1979; Stiles and Hahs, 1991). Consequently, irregularities in muscle force keep most body parts in a constant state of oscillation that is barely visible to the unaided eye. This oscillation is the mechanical component of physiologic tremor. The mechanical component of physiologic tremor has a frequency w that depends upon the inertia I and stiffness K of the joint, according to the equation w =VKii (Lakie et al., 1986). Therefore, tremor frequency is increased by added stiffness and decreased by added inertia. Furthermore, the frequency of this passive mechanical oscillation will
* Correspondence to: Dr. RJ. Elble, Department of Neurology, Southern Illinois University School of Medicine, P.O. Box 19643, Springfield, IL 62794-9643, USA. E-mail address: [email protected] Tel.: 217-524-7881 (ext. 3002); fax: 217-524-1903.
vary from joint to joint, depending upon the natural inertia and stiffness. Consequently, the frequency of passive mechanical oscillation at the metacarpophalangeal joint is higher (20-30 Hz) than at the wrist (7-10 Hz) and elbow (3-5 Hz) (Stiles and Randall, 1967; Fox and Randall, 1970; Elble and Randall, 1978). The mechanical component of physiologic tremor exists during complete relaxation (rest tremor), active steady posture (postural tremor), and voluntary movement (kinetic tremor). Rest tremor occurs because the mechanical shock of cardiac systole perturbs the body into oscillation (Brumlik and Yap, 1970). These cardioballistic oscillations also contribute to physiologic action tremor (Elble and Randall, 1978), but the relative magnitude of this contribution depends upon the level of voluntary motor activity and varies with the site of recording. Postural head tremor is largely cardioballistic (Fig. 1), while cardioballistics play a minor role in postural hand tremor (Marsden et aI., 1969; Elble and Randall, 1978). The contribution of cardioballistics to physiologic tremor has been studied extensively by looking for mathematical correlation or coherence between the tremor and the timing of cardiac systole, as measured with the electrocardiogram (Marsden et aI., 1969; Elble and Randall, 1978). However, the contribution of cardioballistics is not routinely quantified in measurements of physiologic tremor. Physiologic tremor is barely visible to the unaided eye. Hand tremor is most visible in the extended fingers and may not be visible at the wrist. Physiologic hand tremor is only symptomatic during fine motor tasks requiring great precision, as in microvascular surgery (Harwell and Ferguson, 1983). Normal postural hand tremor recorded 10 em from the wrist contains rhythmic oscillations with a mean peak-to-peak amplitude of 0.009-0.153 mm displacement and 3-33 cm/s' acceleration (Elble, 1986). These mean amplitudes overlap somewhat
358
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Fig. 1. Five-second recordings of head tremor and electrocardiogram (EKG) were obtained from a healthy 80-year-old woman while she sat quietly in a chair. Tremor was measured with a triaxial accelerometer attached to her forehead. Lateral (side-to-side) acceleration is shown in the upper graph. Note the transient increase in acceleration (arrows) following each QRS complex of the EKG, typical of cardioballistic oscillation.
with the lower range of mild essential tremor (Elble, 1986). 22.2. Neurogenic oscillation
Motor unit firing is largely asynchronous during steady muscle contractions. Consequently, the Fourier power spectrum of the rectified-filtered EMG is statistically flat (Fig. 2). Two or more motor units may discharge synchronously (within a few milliseconds) during steady voluntary contractions, but this short-term synchronization occurs intermittently for a few milliseconds and affects only 8% of motor unit discharges (Dietz et al., 1976; Dengler et al., 1984; Datta et al., 1991; De Luca et al., 1993; Semmler and Nordstrom, 1998). The degree to which short-term synchronization contributes to physiologic tremor has not been quantified, and the mechanism of short-term synchronization is uncertain. Some authors believe that this synchronization is due to the joint occurrence of excitatory postsynaptic potentials evoked in multiple motoneurons by branches of a corticospinal fiber (Sears and Stagg, 1976; Datta and Stephens, 1990; Datta et al., 1991; Farmer et al., 1997), while others favor a role
for central oscillatory drive to the motoneuron pool (De Luca et al., 1993). Sensory feedback is not necessary for short-term synchronization (Farmer et al., 1993; Farmer et al., 1997). Rhythmic oscillations in volitional muscle contraction were observed more than 100 years ago by Schafer et al. (1886). The 8-12 Hz component of physiologic tremor is produced by bursts of motorunit discharge at 8-12 Hz. These bursts are produced by synchronous 8-12 Hz modulation of motor unit firing, such that double (paired) discharges, with interspike intervals of 10-40 ms, tend to occur during a cycle of tremor (Elble and Randall, 1976; Kakuda et al., 1999; Wessberg and Kakuda, 1999). The mean firing frequency of participating motor units ranges from 8 to 25 spikes/so Short-term synchronization of motor units does not contribute significantly (Farmer et al., 1993). The frequency of 8-12 Hz entrainment is independent of reflex arc length and is not reduced by increased limb inertia (Fox and Randall, 1970; Stephens and Taylor, 1974; Elble and Randall, 1976; Elble and Randall, 1978). Furthermore, the stretch reflex response to joint perturbation is too weak and too delayed to account for this entrainment (Wessberg and Vallbo, 1996). Therefore, this tremor is believed to emerge from a central source of oscillation. The inferior olive is the most frequently hypothesized source of 8-12 Hz tremor, but this hypothesis is largely conjectural, based on the similarities between this tremor and the 8-12 Hz harmaline tremor in laboratory primates (Elble, 1998a). Other sources of rhythmicity (e.g. thalamus and cortex) are also possible. Koster et al. (1998) found that the 8-12 Hz tremor, enhanced by salbutamol, was coherent between the two forearms in three patients with the syndrome of persistent mirror movements. As these patients are believed to have ipsilateral and contralateral corticospinal projections, Koster's data suggest that that enhanced physiologic tremor is conducted through corticospinal pathways. Corticospinal involvement is supported by the recent finding of coherence between the 8-12 Hz tremor and EEG (Raethjen et al., 2000a). However, the primary source of oscillation is still uncertain. Elble (2003) quantified hand tremor and forearm EMG in 100 healthy adults, aged 20-40, and 100 older adults, aged 70-90, and Raethjen et al. (2000b) quantified hand tremor and finger tremor in 117 normal people, aged 20-94 years. All of these
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Fig. 2. Autospectra of hand tremor and rectified-filtered extensor carpi radialis brevis EMG recorded with (thin lines) and without (thick lines) a 500-gram load on the hand. Tremor was recorded with an accelerometer and skin electrodes during horizontal extension of the hand, with forearm supported. The frequency of physiologic tremor (left column graphs) decreased with 500-gram loading, and there was no associated peak in the EMG spectrum (i.e. no evidence of motor-unit entrainment). The frequency of enhanced physiologic tremor in a patient with thyrotoxicosis (right column graphs) also decreased with mass loading, but this tremor was associated with a significant peak in the EMG spectrum (arrows).
normal controls exhibited the mechanical component of physiologic tremor, usually with no evidence of associated motor unit entrainment. Only about 10% of these controls exhibited 8-12 Hz motor unit entrainment that was strong enough to produce Fourier spectral peaks in the acceleration and rectified-filtered EMG spectra (Fig. 3). The frequency of this neurogenic tremor may be as low as 6-8 Hz in people older than 65 years. This motor unit entrainment is indistinguishable from mild essential tremor, but its relationship to essential tremor is unclear (Elble, 1986). Most, if not all, people exhibit 8-12 Hz bursts of EMG during slow voluntary movements, particularly in the wrist and finger extensors during slow wrist or finger flexion (Wessberg and Vallbo, 1996; Kakuda et al., 1999).
Thus, there is a tendency for 8-12 Hz motor unit entrainment to occur in everyone, but this tendency is too weak in most healthy adults to produce an EMG spectral peak during voluntary horizontal extension of the hand or finger. In a study of finger tremor, Halliday et al. demonstrated the presence of 15-30 Hz motor unit entrainment that was estimated to explain about 20% of finger tremor in this frequency band (Halliday et al., 1999). The contribution of 15-30 Hz motor unit entrainment to tremor in body parts with greater inertia (e.g. hand, forearm) is much smaller and usually not measurable, even with accelerometry. This component of physiologic tremor is believed to emerge from cortical rhythmicity, as detected with EEG and MEG (Conway et al., 1995; Baker et al.,
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Frequency (Hz) Fig. 3. Autospectra of hand tremor and rectified-filtered extensor carpi radialis brevis EMG recorded with (thin lines; right vertical axes) and without (thick lines; left vertical axes) a 300-grarn load were obtained from a neurologically-normal 32-year-old woman. Tremor was recorded with an accelerometer and skin electrodes during horizontal extension of the hand, with forearm supported. With no mass loading, a single peak is found in the acceleration and rectified-filtered EMG spectra. Mass loading reduced the amplitude and frequency of the mechanical resonance oscillation, which disclosed the second oscillation with motor-unit entrainment at 8-12 Hz (arrows). With no mass loading, the two sources of oscillation seemed to resonate at the same frequency.
1997; Salenius et al., 1997; Halliday et al., 1998; Baker et al., 1999). Normal vocal tremor has a frequency of 6-13 Hz and is due to a combination of rhythmic neural drive and mechanical resonance of the larynx (Ludlow et al., 1986; Winholtz and Ramig, 1992). Ocular microtremor has a peak frequency of approximately 80 Hz, reflecting the high-frequency motoneuron entrainment and extraocular muscle dynamics (Bolger et al., 1999; Spauschus et al., 1999). Additional ocular microtremor at 4 and 10Hz may
Enhanced physiologic tremor occurs during fatigue, anxiety and voluntary movement and in response to beta-adrenergic drugs (Stiles, 1976; Logigian et al., 1988; Stiles and Hahs, 1991). Under these circumstances, the amplitude of tremor may increase by a factor of 5 to 20, and the EMG exhibits bursts of motor unit activity at the frequency of tremor (Hagbarth and Young, 1979; Stiles, 1980). These bursts are produced by entrainment of motor units with mean firing frequencies of 8 to 25 spikes/s, and the modulation of individual motor units is such that double (paired) discharges, with interspike intervals of 10-40 ms, tend to occur during a cycle of tremor (Logigian et al., 1988). Enhanced participation of spinal and possibly longloop stretch reflex pathways plays an important role in the entrainment of motor units. In most people, this enhanced physiologic tremor consists of a single rhythmic oscillation that decreases in frequency with inertial loading (Fig. 2). Thus, enhanced physiologic tremor is typically a mechanical-reflex oscillation in which the inertia and stiffness of the joint play a pivotal role determining tremor frequency. However, the 8-12 Hz component of physiologic tremor is also increased by fatigue, anxiety, voluntary movement (e.g. wrist extension-flexion), beta-adrenergic drugs and central nervous system stimulants (Raethjen et al., 2001), and this component of physiologic tremor may be more evident in people with enhanced tremor. The stiffness and damping of the wrist and other joints are not constant; rather they are a function of displacement and velocity. The effective damping ratio of the wrist and other joints of the limbs is less than one (underdamped), making these joints prone to oscillation. Stiffness and damping increase as the displacement and velocity of oscillation decrease (Milner and Cloutier, 1998). These nonlinear mechanical properties tend to attenuate and control oscillation at low magnitudes to which the stretch reflex is relatively insensitive. Stiffness and damping also increase with increased muscle activation (Milner and Cloutier, 1998), which explains the common
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strategy of antagonistic muscle co-contraction when stability is threatened. The frequency of enhanced mechanical-reflex tremor decreases as the amplitude increases, and this can be explained, at least partially, by a reduction in the mechanical stiffness that occurs when the amplitude of joint oscillation increases (Gottlieb and Agarwal, 1977; Agarwal and Gottlieb, 1984; Lakie et aI., 1984; Zahalak and Pramod, 1985; Milner and Cloutier, 1998). The reduction in tremor frequency with increased amplitude produces a greater phase advance of sensory feedback on tremor, and this results in greater reflex damping, which is beneficial in the control of tremor (Stiles and Hahs, 1991). Stretch-reflex responses can destabilize the wrist and similar joints at frequencies of 7 Hz or greater (Milner and Cloutier, 1998). People with deafferented limbs exhibit irregular broad-band errors in limb position that exceed the amplitude of physiologic and enhanced physiologic tremor, but they do not exhibit the increased tremor with rhythmic motor unit entrainment seen in patients with enhanced mechanical-reflex tremor (Sanes, 1985). Thus, the presence of sensory feedback is not deleterious in terms of the overall amplitude of positional error, rather sensory feedback seems to entrain or concentrate error at a particular frequency, resulting in rhythmic oscillation. The stretch reflex probably contributes to most, if not all, pathologic tremors in this manner, even when a tremor emerges from a central source of oscillation. With greater involvement of segmental and longloop reflexes, the reflex stiffness, damping and loop time play an increasingly important role in determining tremor frequency, while the influence of limb mechanics on tremor frequency diminishes. Consequently, enhanced mechanical-reflex tremor has a frequency that is less dependent upon limb mechanics and more dependent upon reflex loop properties than normal mechanical tremor (Stiles, 1980). This is nicely illustrated in mathematical models of mechanical-reflex tremor (Stein and Oguztoreli, 1976; Bock and Wenderoth, 1999). In these models, the frequency of mechanical-reflex tremor is nearly independent of limb stiffness and inertia when mechanical damping and stiffness are very small relative to stretch-reflex damping and stiffness. Therefore, in the situation of large reflex gain, a mechanical-reflex oscillation may be difficult to
distinguish from a central oscillation on the basis of the frequency response to mechanical loading. However, the mechanical-reflex tremor frequency is still a function of reflex arc length (latency) (Bock and Wenderoth, 1999) and thereby differs from the 8-12 Hz component of physiologic tremor and from essential and Parkinson tremors (Deuschl et al., 1996). 22.4. Clinical guidelines The EMG and mechanical-loading properties of physiologic tremor are of value in the electrophysiologic analysis of action tremor of uncertain etiology. However, the following guidelines and caveats are noteworthy: (1) A tremor whose frequency varies predictably
with mechanical load or reflex arc length is produced, at least in part, by mechanical-reflex mechanisms. A tremor whose frequency is independent of mechanical load and reflex arc length most likely emerges from a central source of oscillation. (2) Tremor with the EMG, amplitude and frequency properties of physiologic tremor or enhanced mechanical-reflex tremor may be recorded from patients with intermittent or very mild action tremor of central origin (e.g. essential tremor, Parkinson tremor) (Deuschl et al., 1996; Deuschl and Elble, 2000). The motor-unit entrainment in a mild pathologic tremor of central origin can be so irregular or intermittent that the bursts of motor-unit activity simply perturb the limb, producing an enhanced mechanical-reflex oscillation (Elble, 1991). A sustained rhythmic motor-unit entrainment is needed to produce an EMG spectral peak that is frequency-invariant with mechanical loading. (3) The significance of a prominent unenhanced 8-12 Hz tremor is unclear. Identical tremor can be recorded from patients with mild essential tremor (Elble, 1986) and Parkinson disease (Lance et al., 1963), and many ostensibly normal older people (age >70) may exhibit a slightly lower tremor frequency of 6--8Hz (Elble, 1998b), making this tremor virtually indistinguishable from mild essential tremor. Since a prominent 8-12 Hz tremor is found in about 10% of controls, its presence should raise the clinical suspicion of an underlying neurologic disorder.
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(4) Some pathologic tremors exhibit the electrophysiologic characteristics of a mechanicalreflex oscillation (e.g. cerebellar outflow tract tremors) (Elble et aI., 1984; Qureshi et aI., 1996). 22.5. Summary Normal action tremor in the upper extremity consists primarily of two rhythmic oscillations, mechanical-reflex and 8-12 Hz (Elble and Randall, 1978; Timmer et aI., 1998). The 8-12 Hz component of physiologic tremor is produced by rhythmic motor-unit entrainment at 8-12 Hz although seemingly normal elderly people exhibit frequencies as low as 6-8 Hz. The frequency of this component is not affected by changes in limb mechanics (inertia and stiffness) or reflex arc length, and it is therefore believed to emerge from a central source of oscillation, the identity of which is unknown. The mechanical-reflex component is so named because its frequency is a function of the inertia and stiffness of the limb and its reflex arc, and when the stretch reflex is enhanced, the frequency of tremor is also a function of reflex arc length. Irregularities in motor unit firing and cardioballistics provide a broadfrequency forcing to the limb, resulting in mechanical-reflex oscillation. The mechanical-reflex oscillation is associated with motor-unit entrainment when its amplitude becomes large enough to induce reflex modulation of motor-unit discharge or when the sensitivity of the reflex arc is increased by such factors as drugs, fatigue, and anxiety. This enhanced mechanical-reflex oscillation is the primary source of enhanced physiologic tremor although the 8-12 Hz component is also enhanced by these factors.
Acknowledgment This work was supported by the Spastic Paralysis Research Foundation of Kiwanis International, Illinois-Eastern Iowa District.
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357 CHAPTER 22
Physiologic and enhanced physiologic tremor Rodger J. Elble* Department of Neurology, Southern Illinois University School of Medicine, P.O. Box 19643, Springfield, 1L 62794-9643, USA
Healthy people exhibit rhythmic oscillations in body position and muscle contraction, and these oscillations are called physiologic tremor. The mechanisms of physiologic tremor are reviewed in this chapter.
22.1. Passive mechanical oscillation The friction and viscous damping in most joints are not sufficient to prevent passive mechanical oscillation in response to a perturbation. Skeletal muscle behaves as a low-pass filter in response to motor-unit excitation, and this filtering effect limits the fluctuations in muscle force caused by irregularities in motor unit firing (Stein and Oguztoreli, 1976). However, these irregularities are not filtered completely, and they continuously perturb associated joints into oscillation. Muscle-spindle and tendonorgan reflex loops lack the sensitivity to attenuate these small oscillations, and the underdamped mechanical properties of most joints are conducive to oscillation (Hagbarth and Young, 1979; Stiles and Hahs, 1991). Consequently, irregularities in muscle force keep most body parts in a constant state of oscillation that is barely visible to the unaided eye. This oscillation is the mechanical component of physiologic tremor. The mechanical component of physiologic tremor has a frequency w that depends upon the inertia I and stiffness K of the joint, according to the equation w =VKii (Lakie et al., 1986). Therefore, tremor frequency is increased by added stiffness and decreased by added inertia. Furthermore, the frequency of this passive mechanical oscillation will
* Correspondence to: Dr. RJ. Elble, Department of Neurology, Southern Illinois University School of Medicine, P.O. Box 19643, Springfield, IL 62794-9643, USA. E-mail address: [email protected] Tel.: 217-524-7881 (ext. 3002); fax: 217-524-1903.
vary from joint to joint, depending upon the natural inertia and stiffness. Consequently, the frequency of passive mechanical oscillation at the metacarpophalangeal joint is higher (20-30 Hz) than at the wrist (7-10 Hz) and elbow (3-5 Hz) (Stiles and Randall, 1967; Fox and Randall, 1970; Elble and Randall, 1978). The mechanical component of physiologic tremor exists during complete relaxation (rest tremor), active steady posture (postural tremor), and voluntary movement (kinetic tremor). Rest tremor occurs because the mechanical shock of cardiac systole perturbs the body into oscillation (Brumlik and Yap, 1970). These cardioballistic oscillations also contribute to physiologic action tremor (Elble and Randall, 1978), but the relative magnitude of this contribution depends upon the level of voluntary motor activity and varies with the site of recording. Postural head tremor is largely cardioballistic (Fig. 1), while cardioballistics play a minor role in postural hand tremor (Marsden et aI., 1969; Elble and Randall, 1978). The contribution of cardioballistics to physiologic tremor has been studied extensively by looking for mathematical correlation or coherence between the tremor and the timing of cardiac systole, as measured with the electrocardiogram (Marsden et aI., 1969; Elble and Randall, 1978). However, the contribution of cardioballistics is not routinely quantified in measurements of physiologic tremor. Physiologic tremor is barely visible to the unaided eye. Hand tremor is most visible in the extended fingers and may not be visible at the wrist. Physiologic hand tremor is only symptomatic during fine motor tasks requiring great precision, as in microvascular surgery (Harwell and Ferguson, 1983). Normal postural hand tremor recorded 10 em from the wrist contains rhythmic oscillations with a mean peak-to-peak amplitude of 0.009-0.153 mm displacement and 3-33 cm/s' acceleration (Elble, 1986). These mean amplitudes overlap somewhat
358
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Fig. 1. Five-second recordings of head tremor and electrocardiogram (EKG) were obtained from a healthy 80-year-old woman while she sat quietly in a chair. Tremor was measured with a triaxial accelerometer attached to her forehead. Lateral (side-to-side) acceleration is shown in the upper graph. Note the transient increase in acceleration (arrows) following each QRS complex of the EKG, typical of cardioballistic oscillation.
with the lower range of mild essential tremor (Elble, 1986). 22.2. Neurogenic oscillation
Motor unit firing is largely asynchronous during steady muscle contractions. Consequently, the Fourier power spectrum of the rectified-filtered EMG is statistically flat (Fig. 2). Two or more motor units may discharge synchronously (within a few milliseconds) during steady voluntary contractions, but this short-term synchronization occurs intermittently for a few milliseconds and affects only 8% of motor unit discharges (Dietz et al., 1976; Dengler et al., 1984; Datta et al., 1991; De Luca et al., 1993; Semmler and Nordstrom, 1998). The degree to which short-term synchronization contributes to physiologic tremor has not been quantified, and the mechanism of short-term synchronization is uncertain. Some authors believe that this synchronization is due to the joint occurrence of excitatory postsynaptic potentials evoked in multiple motoneurons by branches of a corticospinal fiber (Sears and Stagg, 1976; Datta and Stephens, 1990; Datta et al., 1991; Farmer et al., 1997), while others favor a role
for central oscillatory drive to the motoneuron pool (De Luca et al., 1993). Sensory feedback is not necessary for short-term synchronization (Farmer et al., 1993; Farmer et al., 1997). Rhythmic oscillations in volitional muscle contraction were observed more than 100 years ago by Schafer et al. (1886). The 8-12 Hz component of physiologic tremor is produced by bursts of motorunit discharge at 8-12 Hz. These bursts are produced by synchronous 8-12 Hz modulation of motor unit firing, such that double (paired) discharges, with interspike intervals of 10-40 ms, tend to occur during a cycle of tremor (Elble and Randall, 1976; Kakuda et al., 1999; Wessberg and Kakuda, 1999). The mean firing frequency of participating motor units ranges from 8 to 25 spikes/so Short-term synchronization of motor units does not contribute significantly (Farmer et al., 1993). The frequency of 8-12 Hz entrainment is independent of reflex arc length and is not reduced by increased limb inertia (Fox and Randall, 1970; Stephens and Taylor, 1974; Elble and Randall, 1976; Elble and Randall, 1978). Furthermore, the stretch reflex response to joint perturbation is too weak and too delayed to account for this entrainment (Wessberg and Vallbo, 1996). Therefore, this tremor is believed to emerge from a central source of oscillation. The inferior olive is the most frequently hypothesized source of 8-12 Hz tremor, but this hypothesis is largely conjectural, based on the similarities between this tremor and the 8-12 Hz harmaline tremor in laboratory primates (Elble, 1998a). Other sources of rhythmicity (e.g. thalamus and cortex) are also possible. Koster et al. (1998) found that the 8-12 Hz tremor, enhanced by salbutamol, was coherent between the two forearms in three patients with the syndrome of persistent mirror movements. As these patients are believed to have ipsilateral and contralateral corticospinal projections, Koster's data suggest that that enhanced physiologic tremor is conducted through corticospinal pathways. Corticospinal involvement is supported by the recent finding of coherence between the 8-12 Hz tremor and EEG (Raethjen et al., 2000a). However, the primary source of oscillation is still uncertain. Elble (2003) quantified hand tremor and forearm EMG in 100 healthy adults, aged 20-40, and 100 older adults, aged 70-90, and Raethjen et al. (2000b) quantified hand tremor and finger tremor in 117 normal people, aged 20-94 years. All of these
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Fig. 2. Autospectra of hand tremor and rectified-filtered extensor carpi radialis brevis EMG recorded with (thin lines) and without (thick lines) a 500-gram load on the hand. Tremor was recorded with an accelerometer and skin electrodes during horizontal extension of the hand, with forearm supported. The frequency of physiologic tremor (left column graphs) decreased with 500-gram loading, and there was no associated peak in the EMG spectrum (i.e. no evidence of motor-unit entrainment). The frequency of enhanced physiologic tremor in a patient with thyrotoxicosis (right column graphs) also decreased with mass loading, but this tremor was associated with a significant peak in the EMG spectrum (arrows).
normal controls exhibited the mechanical component of physiologic tremor, usually with no evidence of associated motor unit entrainment. Only about 10% of these controls exhibited 8-12 Hz motor unit entrainment that was strong enough to produce Fourier spectral peaks in the acceleration and rectified-filtered EMG spectra (Fig. 3). The frequency of this neurogenic tremor may be as low as 6-8 Hz in people older than 65 years. This motor unit entrainment is indistinguishable from mild essential tremor, but its relationship to essential tremor is unclear (Elble, 1986). Most, if not all, people exhibit 8-12 Hz bursts of EMG during slow voluntary movements, particularly in the wrist and finger extensors during slow wrist or finger flexion (Wessberg and Vallbo, 1996; Kakuda et al., 1999).
Thus, there is a tendency for 8-12 Hz motor unit entrainment to occur in everyone, but this tendency is too weak in most healthy adults to produce an EMG spectral peak during voluntary horizontal extension of the hand or finger. In a study of finger tremor, Halliday et al. demonstrated the presence of 15-30 Hz motor unit entrainment that was estimated to explain about 20% of finger tremor in this frequency band (Halliday et al., 1999). The contribution of 15-30 Hz motor unit entrainment to tremor in body parts with greater inertia (e.g. hand, forearm) is much smaller and usually not measurable, even with accelerometry. This component of physiologic tremor is believed to emerge from cortical rhythmicity, as detected with EEG and MEG (Conway et al., 1995; Baker et al.,
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Frequency (Hz) Fig. 3. Autospectra of hand tremor and rectified-filtered extensor carpi radialis brevis EMG recorded with (thin lines; right vertical axes) and without (thick lines; left vertical axes) a 300-grarn load were obtained from a neurologically-normal 32-year-old woman. Tremor was recorded with an accelerometer and skin electrodes during horizontal extension of the hand, with forearm supported. With no mass loading, a single peak is found in the acceleration and rectified-filtered EMG spectra. Mass loading reduced the amplitude and frequency of the mechanical resonance oscillation, which disclosed the second oscillation with motor-unit entrainment at 8-12 Hz (arrows). With no mass loading, the two sources of oscillation seemed to resonate at the same frequency.
1997; Salenius et al., 1997; Halliday et al., 1998; Baker et al., 1999). Normal vocal tremor has a frequency of 6-13 Hz and is due to a combination of rhythmic neural drive and mechanical resonance of the larynx (Ludlow et al., 1986; Winholtz and Ramig, 1992). Ocular microtremor has a peak frequency of approximately 80 Hz, reflecting the high-frequency motoneuron entrainment and extraocular muscle dynamics (Bolger et al., 1999; Spauschus et al., 1999). Additional ocular microtremor at 4 and 10Hz may
Enhanced physiologic tremor occurs during fatigue, anxiety and voluntary movement and in response to beta-adrenergic drugs (Stiles, 1976; Logigian et al., 1988; Stiles and Hahs, 1991). Under these circumstances, the amplitude of tremor may increase by a factor of 5 to 20, and the EMG exhibits bursts of motor unit activity at the frequency of tremor (Hagbarth and Young, 1979; Stiles, 1980). These bursts are produced by entrainment of motor units with mean firing frequencies of 8 to 25 spikes/s, and the modulation of individual motor units is such that double (paired) discharges, with interspike intervals of 10-40 ms, tend to occur during a cycle of tremor (Logigian et al., 1988). Enhanced participation of spinal and possibly longloop stretch reflex pathways plays an important role in the entrainment of motor units. In most people, this enhanced physiologic tremor consists of a single rhythmic oscillation that decreases in frequency with inertial loading (Fig. 2). Thus, enhanced physiologic tremor is typically a mechanical-reflex oscillation in which the inertia and stiffness of the joint play a pivotal role determining tremor frequency. However, the 8-12 Hz component of physiologic tremor is also increased by fatigue, anxiety, voluntary movement (e.g. wrist extension-flexion), beta-adrenergic drugs and central nervous system stimulants (Raethjen et al., 2001), and this component of physiologic tremor may be more evident in people with enhanced tremor. The stiffness and damping of the wrist and other joints are not constant; rather they are a function of displacement and velocity. The effective damping ratio of the wrist and other joints of the limbs is less than one (underdamped), making these joints prone to oscillation. Stiffness and damping increase as the displacement and velocity of oscillation decrease (Milner and Cloutier, 1998). These nonlinear mechanical properties tend to attenuate and control oscillation at low magnitudes to which the stretch reflex is relatively insensitive. Stiffness and damping also increase with increased muscle activation (Milner and Cloutier, 1998), which explains the common
PHYSIOLOGIC AND ENHANCED PHYSIOLOGIC TREMOR
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strategy of antagonistic muscle co-contraction when stability is threatened. The frequency of enhanced mechanical-reflex tremor decreases as the amplitude increases, and this can be explained, at least partially, by a reduction in the mechanical stiffness that occurs when the amplitude of joint oscillation increases (Gottlieb and Agarwal, 1977; Agarwal and Gottlieb, 1984; Lakie et aI., 1984; Zahalak and Pramod, 1985; Milner and Cloutier, 1998). The reduction in tremor frequency with increased amplitude produces a greater phase advance of sensory feedback on tremor, and this results in greater reflex damping, which is beneficial in the control of tremor (Stiles and Hahs, 1991). Stretch-reflex responses can destabilize the wrist and similar joints at frequencies of 7 Hz or greater (Milner and Cloutier, 1998). People with deafferented limbs exhibit irregular broad-band errors in limb position that exceed the amplitude of physiologic and enhanced physiologic tremor, but they do not exhibit the increased tremor with rhythmic motor unit entrainment seen in patients with enhanced mechanical-reflex tremor (Sanes, 1985). Thus, the presence of sensory feedback is not deleterious in terms of the overall amplitude of positional error, rather sensory feedback seems to entrain or concentrate error at a particular frequency, resulting in rhythmic oscillation. The stretch reflex probably contributes to most, if not all, pathologic tremors in this manner, even when a tremor emerges from a central source of oscillation. With greater involvement of segmental and longloop reflexes, the reflex stiffness, damping and loop time play an increasingly important role in determining tremor frequency, while the influence of limb mechanics on tremor frequency diminishes. Consequently, enhanced mechanical-reflex tremor has a frequency that is less dependent upon limb mechanics and more dependent upon reflex loop properties than normal mechanical tremor (Stiles, 1980). This is nicely illustrated in mathematical models of mechanical-reflex tremor (Stein and Oguztoreli, 1976; Bock and Wenderoth, 1999). In these models, the frequency of mechanical-reflex tremor is nearly independent of limb stiffness and inertia when mechanical damping and stiffness are very small relative to stretch-reflex damping and stiffness. Therefore, in the situation of large reflex gain, a mechanical-reflex oscillation may be difficult to
distinguish from a central oscillation on the basis of the frequency response to mechanical loading. However, the mechanical-reflex tremor frequency is still a function of reflex arc length (latency) (Bock and Wenderoth, 1999) and thereby differs from the 8-12 Hz component of physiologic tremor and from essential and Parkinson tremors (Deuschl et al., 1996). 22.4. Clinical guidelines The EMG and mechanical-loading properties of physiologic tremor are of value in the electrophysiologic analysis of action tremor of uncertain etiology. However, the following guidelines and caveats are noteworthy: (1) A tremor whose frequency varies predictably
with mechanical load or reflex arc length is produced, at least in part, by mechanical-reflex mechanisms. A tremor whose frequency is independent of mechanical load and reflex arc length most likely emerges from a central source of oscillation. (2) Tremor with the EMG, amplitude and frequency properties of physiologic tremor or enhanced mechanical-reflex tremor may be recorded from patients with intermittent or very mild action tremor of central origin (e.g. essential tremor, Parkinson tremor) (Deuschl et al., 1996; Deuschl and Elble, 2000). The motor-unit entrainment in a mild pathologic tremor of central origin can be so irregular or intermittent that the bursts of motor-unit activity simply perturb the limb, producing an enhanced mechanical-reflex oscillation (Elble, 1991). A sustained rhythmic motor-unit entrainment is needed to produce an EMG spectral peak that is frequency-invariant with mechanical loading. (3) The significance of a prominent unenhanced 8-12 Hz tremor is unclear. Identical tremor can be recorded from patients with mild essential tremor (Elble, 1986) and Parkinson disease (Lance et al., 1963), and many ostensibly normal older people (age >70) may exhibit a slightly lower tremor frequency of 6--8Hz (Elble, 1998b), making this tremor virtually indistinguishable from mild essential tremor. Since a prominent 8-12 Hz tremor is found in about 10% of controls, its presence should raise the clinical suspicion of an underlying neurologic disorder.
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(4) Some pathologic tremors exhibit the electrophysiologic characteristics of a mechanicalreflex oscillation (e.g. cerebellar outflow tract tremors) (Elble et aI., 1984; Qureshi et aI., 1996). 22.5. Summary Normal action tremor in the upper extremity consists primarily of two rhythmic oscillations, mechanical-reflex and 8-12 Hz (Elble and Randall, 1978; Timmer et aI., 1998). The 8-12 Hz component of physiologic tremor is produced by rhythmic motor-unit entrainment at 8-12 Hz although seemingly normal elderly people exhibit frequencies as low as 6-8 Hz. The frequency of this component is not affected by changes in limb mechanics (inertia and stiffness) or reflex arc length, and it is therefore believed to emerge from a central source of oscillation, the identity of which is unknown. The mechanical-reflex component is so named because its frequency is a function of the inertia and stiffness of the limb and its reflex arc, and when the stretch reflex is enhanced, the frequency of tremor is also a function of reflex arc length. Irregularities in motor unit firing and cardioballistics provide a broadfrequency forcing to the limb, resulting in mechanical-reflex oscillation. The mechanical-reflex oscillation is associated with motor-unit entrainment when its amplitude becomes large enough to induce reflex modulation of motor-unit discharge or when the sensitivity of the reflex arc is increased by such factors as drugs, fatigue, and anxiety. This enhanced mechanical-reflex oscillation is the primary source of enhanced physiologic tremor although the 8-12 Hz component is also enhanced by these factors.
Acknowledgment This work was supported by the Spastic Paralysis Research Foundation of Kiwanis International, Illinois-Eastern Iowa District.
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