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Mov Disord. Author manuscript; available in PMC 2010 June 8.
Published in final edited form as:
PMCID: PMC2882027
EMSID: UKMS30693

SLOW ORTHOSTATIC TREMOR IN MULTIPLE SCLEROSIS

While several forms of tremor are common in multiple sclerosis (MS), orthostatic tremor (OT) has not been reported20.

A 38 year old female, diagnosed with clinically definite relapsing remitting MS at the age of 27, presented following initial improvement from a relapse affecting ambulation, complaining of tremor affecting her legs associated with an intense feeling of unsteadiness. The tremor was not present when sitting but appeared upon standing (see video). It was reduced but not relieved by walking. Neurological examination demonstrated increased tone in the legs, ankle clonus, pyramidal weakness in the left leg (MRC grade 4), symmetrical hyperreflexia, extensor plantar responses, mild left upper limb dysmetria, mild bilateral heel-shin ataxia, impaired proprioception at the hallux bilaterally and absent vibration sense to the knee. These examination findings had remained stable for several years (outside of acute relapses) and until she developed OT had not prevented independent ambulation.

MRI showed active disease with several periventricular lesions in frontal and parietal cortex, and one lesion within the left brachium pontis (Figure A), which enhanced with gadolinium (Figure B).

Figure
Radiology and clinical neurophysiology

Electrophysiology showed no evidence of axial or appendicular tremor while seated, but as the patient stood tremor appeared in the legs and trunk. The tremor power spectrum obtained from an accelerometer affixed to the left patella (Figure C) showed a dominant peak at ~4Hz and a smaller sub-harmonic at ~8Hz. Raw rectified EMG recorded using adhesive electrodes from left tibialis anterior (gain 500-5000; band pass filtered 30Hz-2kHz; 5kHz digitization) whilst standing contained four 100ms bursts of EMG per second (Figure D). Frequency domain analysis (see normalised power spectra in Figure E) confirmed that the dominant frequency was ~4Hz. In the left gastrocnemius-soleus and tibialis anterior power spectra there were small additional 8-15Hz sub-peaks. Coherence analysis (see1415) confirmed that there was significant unilateral and bilateral EMG-EMG coherence not only at tremor frequency but also in the 8-12Hz and 13-18Hz ranges, suggesting that other common frequencies might also be driving lower limb tremor (Figure F).

The effects of patella tendon stimulation on OT were also investigated (Figure G). The linear relationship between tremor phase before and after a tendon tap confirmed that this form of muscle afferent stimulation could not reset the phase of the tremor, as previously described in slow4 and fast OT16, 17.

Pharmacological treatment (i.e. clonazepam, levetiracetam, L-DOPA, gabapentin) was either ineffective or produced intolerable side effects.

Orthostatic tremor (OT) is a rare form of action tremor affecting the legs and trunk. It appears on standing, is associated with a profound and disabling sense of unsteadiness and is relieved by sitting, walking or the use of a support. Two types of OT are recognized: fast OT, characterised by bursts of muscle activity at 13-18 Hz 1-3; and slow OT 4, 5, with a frequency of 3-8 Hz.

Slow OT was first described in 1986 in a family with essential tremor5. Subsequently it has been described in patients with Parkinson’s disease and parkinsonism6-8, and in one patient two months after resection of a cavernoma involving the right brachium pontis9 (cf. Figure A-B). Idiopathic slow OT, in the absence of primary or associated neurological disease has also been described 4.

In slow OT EMG recordings from leg, trunk and arm muscles demonstrate regular 70-120 ms bursts of activity in the 4-6 Hz range8. Coherence analysis reveals powerful coupling between EMG recorded from lower limb, upper limb and axial muscles both unilaterally and bilaterally, at tremor frequency, which is absent in controls under normal conditions 10 and patients with orthostatic myoclonus 8. Treatment with clonazepam is reportedly helpful; if there is associated parkinsonism anecdotal evidence to supports the use of L-dopa, dopamine receptor agonists or trihexyphenidyl, with or without clonazepam 11, 12.

Although OT has not previously been described in MS, the spastic-ataxic gait sometimes encountered in MS can be mistaken for OT22. This is partly because of the subjective sense of unsteadiness, but also because the frequency of clonus (~4 Hz) 23 can resemble tremor. Clonus, which is easily re-set by stimulating muscle afferents 24, did not contribute to the OT observed in our patient because her tremor could not be entrained by tendon vibration (see Fig. G).

Acknowledgement

Funded by The Wellcome Trust.

Research activities of MRB, KMF and SNB are supported by grants from The Wellcome Trust, MRC, BBSRC, EPSRC and UCB Pharma held by SNB.

Footnotes

Disclosure statement

MRB is employed by the NHS and NIHR. MED and HML are NHS employees. SNB and KMF are employees of Newcastle University.

SNB and KMF are engaged as consultants to Cambridge Pharmaceuticals on an unrelated project.

MED has received honoraria from BiogenIdec, Bayer Schering, Merck Serono and Teva.

HML, SNB, MRB and KMF have received travel grants from UCB Pharma.

The authors have no conflict of interest.

Video Legend

A. Standing. Initially the patient is seated and there is no lower limb or axial tremor. As she stands up marked axial and lower limb tremor appears. B. Walking. As the patient walks, with the aid of two sticks, the tremor appears to improve. However, there was no subjective change in the sensation of unsteadiness. C. Lower limb examination. The patient demonstrates evidence of mild heel-shin ataxia, which is worse on the left. D. Co-contraction. While supine the patient was asked to raise her legs with her feet in plantar flexion and to co-contract her leg muscles. During this manoeuvre there is no visible tremor (tremor can only be detected with accelerometry). E. Upper limb examination. Assessment of tremor in the upper limbs only demonstrated mild terminal tremor on the left. F. Eye movements. Only smooth pursuit was tested, which was normal.

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