Abstract
Primary orthostatic tremor is characterized by 16-Hz motor activity that is coherent between muscles. It has been suggested that this tremor originates in the brain. This view is questioned by findings from a patient with complete paraplegia who experiences intermittent leg spasms at rest. The EMG activity within the spasms showed a 16-Hz component that was coherent between muscles unilaterally and bilaterally. This raises the possibility that the spinal cord could be the source of orthostatic tremor.
Tremors are commonly characterized by the frequency of their oscillations. Often there is overlap in the range of tremor frequencies found in different diseases. However, there is one tremor syndrome, primary orthostatic tremor, with a frequency that is virtually pathognomonic. Primary orthostatic tremor is associated with synchronized bursting of muscle activity at a remarkably fast rate of ∼16 Hz.1 Because of its high frequency, the tremor is difficult to see with the naked eye but has a devastating effect on the patient, in whom it produces a profound and disabling sense of unsteadiness when standing.2,3⇓ Patients are compelled to sit down or walk after a short time, ranging from a few seconds to a few minutes depending on the severity of the condition.3 Although orthostatic tremor generally is thought to originate from a central oscillator, it is not known where in the nervous system the oscillator is located. A number of reports have suggested possible supraspinal sites as the origin of this activity,4–9⇓⇓⇓⇓⇓ including the brain stem,5 the motor cortex,6 and the pons and cerebellum,7 although to date no single site has emerged as the origin of this tremor. We show that the human spinal cord, when disconnected from the brain, is capable of generating 16-Hz motor oscillations that are coherent between leg muscles.
Case report.
With local ethical committee approval and the patient’s informed consent, we investigated muscle spasms in a patient with paraplegia resulting from a high fall >20 years ago. The patient suffered a dislocation fracture of the spine and a traumatic complete T10/11 lesion (confirmed radiologically and clinically), resulting in the total absence of sensation and voluntary motor activity below the level of the lesion. At rest (either seated or recumbent), he experiences intermittent spasms that last for 1 or 2 seconds and occur every 1 to 30 seconds. All spasms are bilateral and produce ankle dorsiflexion, knee flexion, and hip flexion. Surface-recorded EMG activity showed synchronous bursts of muscle activity on both sides of the body during a spasm but no activity in the periods between spasms. Figure 1 illustrates the activity recorded from a unilateral pair of muscles separated by a joint (quadriceps and tibialis anterior from the right side) and a bilateral pair of muscles (left and right tibialis anterior). These muscles were chosen as illustrative, but all muscle groups (right and left quadriceps, tibialis anterior, and gastrocnemius) showed a similar pattern of activity.
Figure 1. Movements and muscle activity during spasms recorded with the patient recumbent. Movements were recorded using a contactless optoelectronic measurement system (CODA, Charnwood Dynamics, Leicester, UK). Top trace shows foot movement, which was obtained by measuring the movement of a marker placed on the great toe relative to another placed on the ankle. The negative-going deflections indicate a movement of the foot toward the knee. Bottom three traces show EMG activity from three sample muscles of the right and left legs.
Closer inspection of the EMG activity during a spasm often revealed fluctuating or oscillatory behavior. Figure 2 shows an example of raw EMG (MIE Medical Ltd., Leeds, UK) and rectified, low-pass filtered EMG (low-pass at 50 Hz) from the right tibialis anterior during a spasm. Oscillations are evident in the filtered signal. To study these oscillations further, the EMG activity recorded during spasms was spectrally analyzed using a Fourier approach.8 Signals were sampled at 1 kHz, and analysis was performed on 124 nonoverlapping samples of length 512, giving a frequency resolution of 1.95 Hz. Analysis was performed using Matlab (Mathworks, Cambridge, UK) and Neurospec (www.neurospec.org). Confidence limits were estimated using a previously published technique.8
Figure 2. Raw (A) and rectified and smoothed (B) EMG from the right tibialis anterior muscle during a spasm. Clear oscillatory activity is visible in the rectified and smoothed trace (low-pass filtered at 50 Hz; there is also a short time delay at the start of the record caused by the filter characteristics). Similar oscillatory behavior was visible in the muscle groups recorded in this study.
Autospectra of the EMG activity from the right quadriceps and the right and left tibialis anterior are shown in figure 3. Clear peaks of activity at ∼16 Hz can be seen in muscles of the right leg. Also shown in figure 3 is the coherence between pairs of muscles. Coherence is a measure of the correlation between signals in the frequency domain and is measured on a scale from 0 (no correlation) to unity (perfect correlation) in each frequency bin. The EMG activity was coherent at 16 Hz between the unilateral muscle pair and between the bilateral muscle pair. Coherence at 16 Hz was evident between all combinations of muscle pairs studied. Coherence also was found between the unilateral muscle pair in the 25- to 35-Hz band. Phase plots showed a nonzero linear phase relationship between muscles in each band of coherence. This suggests that there was a consistent time lag between each pair of muscles,8 indicating that the activity did not result from electrical cross-talk. Cross-talk would result in zero-phase lag between the muscles at all frequencies.
Figure 3. Auto spectra (top) of muscle activity from the right quadriceps and left and right tibialis anterior during a muscle spasm. These data were obtained with the patient seated and at rest (in the absence of electrical stimulation) with his legs extended. No stimuli were given to provoke the activity. Records were obtained from 124 segments each of length 512. There is a peak in the spectra at ∼16 Hz in the right quadriceps and tibialis anterior. This peak is not as prominent in the left tibialis anterior. The coherence (bottom) between the muscles shows that ipsilaterally (left) and bilaterally (right) there is significant coherence at 16 Hz. The horizontal line in both plots indicates the 95% CI level. The phase relationships during the periods of significant coherence are shown in the top right corner of the coherence plots.
The spasms in our patient had an oscillatory component at 16 Hz that was coherent between muscles within and between legs. This pattern of coherence suggests that a proportion of the 16-Hz activity originates from a common source. The source is likely to be within the lumbosacral spinal cord because our patient had a complete T10/11 spinal cord lesion. The results should be interpreted with some caution because they were observed in only one of six patients we have studied with similar spinal cord lesions. Although the reason for this difference between patients is unclear, the results from this patient serve to demonstrate that the spinal cord contains circuitry that is capable of oscillating at 16 Hz.
Discussion.
The oscillatory phenomena observed here are reminiscent of orthostatic tremor, although the peaks in the raw EMG are less prominent and the intermuscular coherence values are smaller than for the typical presentation of orthostatic tremor. Nevertheless, the 16-Hz frequency peak and the pattern of intermuscular coherence at this frequency raise the possibility that orthostatic tremor may originate from the spinal cord. However, there are some difficulties with this interpretation. First, the oscillations seen in our patient were present when he was lying or sitting, whereas orthostatic tremor is usually associated with standing posture. However, electrophysiologic studies have reported the presence of orthostatic tremor in the absence of standing.9,10⇓ Second, orthostatic tremor has been observed in patients with supraspinal lesions.5,7⇓ However, findings of this sort do not necessarily point to a supraspinal tremor source. Supraspinal lesions can produce changes in descending control of the cord, which could release a spinal oscillator. Third, the involvement of cranially innervated muscles in orthostatic tremor suggests a supraspinal tremor source.9 However, as conceded by the authors of that study,9 it is also possible that a spinal cord oscillator could engage cranial muscles through inputs from ascending pathways. We believe our results contribute to the debate regarding the origin of 16-Hz orthostatic tremor by showing that the spinal cord is one possible site of 16-Hz oscillations. If the spinal cord is the source of orthostatic tremor, then its expression may depend on abnormal descending control of the cord from supraspinal centers.
Acknowledgments
J.A.N. was funded by the UCL Graduate School.
The authors thank the patient for participating in this study. We also thank Dr. Peter Brown for helpful discussions and Dr. Mike Cassidy for assistance with the spectral analysis.
Footnotes
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The current address for Dr. Norton is Rehabilitation Neuroscience, Department of Biomedical Engineering, Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
- Received June 10, 2003.
- Accepted September 18, 2003.
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