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Summary
A patient with refractory essential tremor of the hands and head/neck refused deep brain stimulation and requested consideration for spinal cord stimulation (SCS). Trial of a cervical SCS system using a basic tonic waveform produced positive outcomes in hand tremor, head-nodding and daily functioning. The patient proceeded to implant and received regular programming sessions. Outcomes were recorded at follow-ups (1, 3, 6, 12, 23 months postimplant) and included patient self-reported changes, clinical observations, handwriting assessments and The Essential Tremor Rating Assessment Scale scores. Trial of a paraesthesia-free burst waveform programme produced a small improvement in head-nodding, without uncomfortable paraesthesias. With continued programming, the patient reported further improvements to tremor and functionality, with minimal tremor remaining at 12–23 months. No major side effects were reported.
- movement disorders (other than parkinsons)
- spinal cord
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Background
Essential tremor is a debilitating condition that is troublesome to manage. The success of pharmacological treatment is limited, with an approximately 50% responder rate. Refractory tremor has few treatment options other than invasive surgical procedures, the most common being thalamic surgery and deep brain stimulation (DBS). Thalamic surgery is reportedly effective in reducing tremor by up to 83%1 2 though it is considered a last resort due to its irreversibility and association with serious complications.3 DBS focuses on the thalamus or related structures though it is reversible and less destructive. The traditional target is the ventral intermediate nucleus of the thalamus (VIM), others include the subthalamic nucleus and structures within the posterior subthalamic area.4 5 Studies report positive results for DBS in epilepsy, cerebral palsy and intentional tremor.6–10 Epidural/subdural motor cortex stimulation has also produced positive effects in a small number of patients with essential tremor.11 Recently, a novel, non-surgical technique of stereotactic MRI-guided thalamic (VIM) ultrasound lesioning (thalamotomy) has been approved for essential tremor.12 13
Spinal cord stimulation (SCS) was commonly used for the treatment of motor disorders in the 1980s with reasonable efficacy.14 To our knowledge, reports of SCS therapy in the treatment of essential tremor are non-existent. With the development of more sophisticated SCS technology, namely increases in coverage and flexibility and greater control afforded by advanced programming features, SCS has a largely untapped potential in the treatment of tremor. This report details a case in which SCS using a cervically implanted 16-electrode system was used to treat a patient with essential tremor of the hands, head and neck who declined DBS.
Case presentation
A woman in her 70s presented to the pain clinic with pelvic pain as her primary symptom. She had a history of detrusor instability of 11 years and essential tremor of 15 years. She had previously seen a neurologist for her essential tremor and had tried propranolol 50 mg two times a day (bd) and topiramate 50 mg at night (nocte) with minor success. DBS was recommended but the patient declined.
Following successful management of the patient’s pelvic pain with prescription of tapentadol SR and a caudal epidural injection of local anaesthetic and steroid combined with pudendal nerve pulsed radio-frequency neurotomy for pain flares, she inquired about neuromodulation for tremor. She was deemed a suitable candidate for a trial of the therapy and underwent the procedure.
Treatment
SCS trial: procedure and preliminary outcomes
The patient was implanted with two eight-contact trial leads spanning the C2–C5 epidural space (figure 1). A basic quadrupole configuration was used with a cathode on the top contacts and an immediately adjacent anode. Using parameters for stimulation outlined by previous studies in tremor management with SCS,14 tonic stimulation using pulse width (PW) of 120 µs and a frequency of 100 Hz was used. The current amplitude (mA) was set to the threshold of perception with the patient able to modulate the intensity of the signal according to comfort. Eight programmes were created with anodes and cathodes on successively lower contacts, such that over an 8-day trial period, the entire length of the electrode, and thereby the C2–C5 cervical span of the spinal cord, could be evaluated in small increments.
Plain film imaging showing cervical lead placement for spinal cord stimulation to treat essential tremor in this patient. Upper: trial; Lower: implant. Left (L) and right (R) sides and cervical segmental levels (C 1, 2, 3) have been labelled.
The patient trialled each programme for 24 hours and, by assessing the degree of hand tremor, head-nodding and functional changes, reported the most effective programme (programme 3). The patient reported improvements in handwriting, head-nodding and her ability to drink water from a cup without a straw.
SCS implant: procedure and programming
Following these positive trial outcomes, the patient proceeded to SCS implantation. The same cervical lead placement was used (figure 1) and a Precision Spectra implantable pulse generator (Boston Scientific, Massachusetts, USA) was implanted in the upper flank. Fourteen programmes were created (PW: 120 µS, frequency: 100 Hz) to identify the most effective electrode configuration and best stimulation locus. Programmes 5 and 7 were found to be most effective. Effectiveness of the programmes was defined as the patient’s subjective choice of most favourable programme(s) which was based on the patient’s ability to function (ie, feeding, drinking, writing), comfort/lack of paraesthesia and confidence (ie, knowing that the patient’s head nodding was less marked).
Evaluations
Outcomes of the therapy were predominantly self-reported. The patient recorded her progress in a diary, demonstrating changes in handwriting and noting changes in tremor and functional capacity (figure 2). Long-term outcomes were assessed using The Essential Tremor Rating Assessment Scale (TETRAS) V1.3, developed by the Tremor Research Group.15
The patient’s handwriting examples: (A) Examples begin at 1 day postimplant (‘P & N’ refers to ‘pins and needles’); (B) A selection of samples from the patient’s diary when the stimulator was switched off; (C) Improvements at 4 months and 5 months postimplant; (D) Examples at 12 months postimplant comparing handwriting when stimulator was turned off, and after 1 min of burst stimulation; (E) The Essential Tremor Rating Assessment Scale (TETRAS) performance subscale handwriting task at 23 months postimplant.
Outcome and follow-up
At 1 month postimplant, a 60% reduction in tremor, particularly head-nodding, and significant improvements to handwriting, were reported. The patient was given the ability to reduce the amplitude of the current to reduce/remove uncomfortable perception of stimulation which was experienced occasionally on most programmes on waking.
At 3 months postimplant, a marked reduction in tremor was reported and demonstrated: tremor and head-nodding returned to baseline levels on turning off the stimulator. The patient requested a trial of a paraesthesia-free programme; hence, burst programming was applied, as described by Pope and colleagues.16 Using the electrode configuration in programmes 5 and 7, a further two programmes were created using a burst waveform with PW 450 µS and interburst frequency 40 Hz (intraburst frequency 290 Hz). No noticeable difference in hand tremor was reported on either burst programme; however, a small but noticeable improvement in head-nodding was reported in the latter programme and without the uncomfortable paraesthesia experienced in the neck and arms.
At 6 months postimplant, the patient was using the stimulator constantly at the perception level and reported minimal remaining tremor and no significant activity-preventing tremor. Residual tremor corresponded with significant emotional stress. The uncomfortable paraesthesia experienced in mornings was mild and did not interfere with functioning. She rated her overall satisfaction with the outcome as a 4 on a Likert scale of 0–5 (where 0=completely dissatisfied and 5=completely satisfied).
At 12 months postimplant, the patient reported the ‘best control’ of her tremor. All but the most effective programme was removed which was duplicated with two additional areas at a higher rate (more pulses at the same subperception level) in an attempt to further remove the residual tremor.
Long-term assessment of the tremor was conducted at a follow-up consultation at 23 months postimplant using TETRAS. The patient performed the assessment with the stimulator turned off (12 hours prior, since the night before) and repeated the assessment 5 min after having the stimulator turned back on. Total test scores improved from 24 to 15 for the activities of daily living subscale, and from 24 to 9.5 for the performance subscale, using a tonic 2 Hz programme run below the threshold for paraesthesia (figure 3). The most significant activity improvements were to feeding (4 vs 0) and writing (3 vs 1). The most improved task performance score was for the left-handed Archimedes spiral task (3 vs 1). Tremor was most improved for head, face and upper limb outstretched and wing-beating assessments.
(A): TETRAS: activities of daily living subscale scores: stimulator off (12 hours prior) versus stimulator on (5 min of tonic 2 Hz programme run below the threshold for paraesthesia). (B) TETRAS: performance subscale scores: stimulator off (12 hours prior) versus stimulator on (5 min of tonic 2 Hz programme run below the threshold for paraesthesia). TETRAS, The Essential Tremor Rating Assessment Scale.
Discussion
Reports on the use of SCS to treat essential tremor are virtually non-existent. The effectiveness of SCS therapy in the treatment of motor disorders is best detailed in a case series of patients with cerebral palsy, dystonia, torticollis or post-traumatic neurological loss who were seen to benefit with a four-electrode multiple level stimulation, with improvements to tremor shown in 62%–85% of patients.14 Later reviews of 1336 cases show that successful symptom relief can be achieved by manipulation of a number of parameters including the stimulated level on the spinal cord, and the programming parameters such as field shape, polarity and frequency of stimulation.17
Stimulation with electrodes placed from C2 to C4 has traditionally shown to be the most efficacious in reducing tremor, with the flexibility of four-electrode systems being preferred to the previous two-electrode systems.18 19 A more recent review on the use of SCS in the treatment of motor disorders, including dystonia, Parkinson’s disease, non-parkinsonian tremors and painful leg and moving toes, has been published20 which noted the lack of publications on the use of SCS in essential tremor and the scarcity of data published regarding tremor in general. Clinical reports on the use of SCS in the treatment of non-parkinsonian tremors are particularly limited. A study of 19 patients with multiple sclerosis and associated tremor who were implanted with a cervical SCS electrode reported improvements to tremor in 11% of patients.21 Recent case reports of SCS for intractable orthostatic tremor have shown that bipolar stimulation in the lower thoracic spine (PW: 120-300 µS, frequency: 130 Hz) produced significant long-term improvements in standing times and unsteadiness,22 23 with outcomes further improved with burst stimulation.24
The mechanism by which SCS may influence tremor is not entirely clear. It is known that cervical SCS can activate dorsal column nuclei (cuneate and gracile nuclei).25 These nuclei have connections to both the periaqueductal grey matter and the red nucleus,26 27 and thus there may be activation of the dentatorubrothalamic tract. This tract appears a successful target in DBS suppression of essential tremor.28–30 It is also possible that more than one mechanism may be involved in cervical SCS suppression of tremor.20
The standard of care for refractory tremor remains DBS. However, if DBS was contraindicated (ie, patient refusal, cortical access issues, previously failed DBS that was technically optimal), then a trial of SCS may be considered. Alternatively, a newly approved therapy for essential tremor (that was not an option at the time of this case) is MRI-guided focused ultrasound thalamotomy.31 This technique involves precise, real-time thermal lesioning of the VIM of the thalamus without the need for surgery. Studies have reported significant improvements using this technique in patients with tremor.13 32
Nevertheless, there are appreciable benefits to SCS therapy for the treatment of refractory essential tremor. Compared with other established therapies, SCS is less invasive than thalamic surgery and DBS, with potential adverse effects being relatively less serious. In comparison with the recently approved non-surgical option of ultrasound thalamotomy, the risk of neurological deficit is lower.13 The most common complications of SCS include lead migration, lead fractures and pain or infection at the implantable pulse generator pocket though these are usually easily resolved. Furthermore, by conducting a minimally invasive and reversible trial of SCS, the patient is able to experience and evaluate the therapy over the short term without committing to an implant; this also serves as a pilot phase for determining optimal lead placement and programming parameters.
This report details the effective use of cervical SCS in the treatment of a case of essential tremor of the head, neck and hands. The patient experienced a significant reduction in tremor during the trial and received an implant. The parameters used for stimulation were guided by previous SCS studies in tremor management.14 During the trial and the first stage of programming the permanent leads, a basic tonic waveform (PW: 120 µS; frequency: 100 Hz) was evaluated and produced positive results. Later, a paraesthesia-free burst waveform programme, as guided by Pope and colleagues,16 was trialled (PW: 450 µS; intraburst frequency: 290 Hz; interburst frequency: 40 Hz) and was found to improve head-nodding, without uncomfortable paraesthesias. With continued optimisation of programming, the patient reported significant improvements to tremor and functionality. No major side effects were reported. The stimulation of the dorsal column at C2–C3 corresponds to the upper limb dermatomes and can result in paraesthesia in the arms and fingertips, depending on the stimulation parameters and the sensitivity of the nerve fibres. The patient can be given the ability to reduce the amplitude of the current to reduce or remove perception of stimulation.
This study is severely limited due to the clinical practice setting and hence retrospective collection of data and lack of quantifiable outcome measures, such as electromyogram (EMG) signals. In order to collect some quantifiable data, we organised a long-term follow-up with the patient to assess her tremor using the clinically validated TETRAS which was completed during a trial of no stimulation versus stimulation on. Future investigations should prospectively collect more robust outcome data, such as by analysing EMG signals and completing TETRAS before SCS trial, post-trial, before implant and at each routine follow-up.
This report provides support, although limited, for the usefulness of SCS in managing essential tremor. Despite the positive results in this case, it is pertinent to remember that 30 years ago, DBS replaced SCS in motor disorder treatment because of its superior results. SCS has improved markedly over the last 30 years but has not gone through the same optimisation process for motor disorders that DBS has. Furthermore, new non-surgical options such as ultrasound thalamotomy have since come to the table. We view SCS as a potential salvage therapy, rather than a direct replacement for DBS. Further research in this area appears warranted.
Learning points
Despite historical support for spinal cord stimulation (SCS) in the treatment of movement disorders and recent advances in the technology, SCS remains a relatively neglected treatment option for tremor.
Cervical SCS has provided long-term symptom relief in a patient with refractory essential tremor of the hands and head/neck who had declined deep brain stimulation.
SCS has several advantages over other advanced treatment options for essential tremor, however further investigations are warranted.
Acknowledgments
The authors would like to thank Wayne H Andreesen for his valuable insight and review of the manuscript.
References
Footnotes
Contributors MR consulted the patient, implanted the stimulator and performed follow-up consultations. US provided assistance with programming of the stimulator and follow-up of the patient. MR, US and DMS contributed to the interpretation of the results and production of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Disclaimer This investigation was neither sponsored nor instigated by Boston Scientific.
Competing interests MR consults for Medtronic, Abbott, Boston Scientific, Nevro Corp, Stimwave, Saluda Medical and Mainstay Medical. He has received travel support from Boston Scientific. US is employed by Boston Scientific Corp as a territory manager in Australia and provided assistance with programming of the stimulator. DMS has no conflicts of interest to declare.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.