Objective Improvement in Orthostatic Tremor Following Spinal Cord Stimulation Demonstrated Using Posturography

Primary orthostatic tremor (OT) is characterized by the presence of a 13–18 Hz high frequency tremor on standing.1, 2 Pharmacotherapy is usually only partially effective. Neuromodulation with deep brain stimulation (DBS) or spinal cord stimulation (SCS) can help in refractory cases. Measures of treatment benefit are limited to clinical assessments, as surface EMG findings typically remain unchanged. We report a patient with refractory OT treated with SCS showing clinical improvement, mirrored by abolition of high frequency movements on posturography. This potentially provides an objective method of assessing treatment response in OT. A 53-year-old woman presented with a 3-month history of progressive subjective unsteadiness on standing. Her symptoms were improved by placing a finger on a stable surface. Neurological examination and nerve conduction studies were normal. Surface EMG detected a 15 Hz tremor of both lower limbs on standing, typical of primary OT. MRI brain and spine were normal. Clonazepam was commenced and uptitrated to 4 mg daily; however, symptoms progressed over 5 years to the point that she stopped working. Due to ongoing progression, she commenced gabapentin at age 62, later switched to pregabalin, as symptomatic therapy. Further medication trials were limited by side effects. At age 65 she had worsening symptoms with increasing social disability. Medication escalation was not tolerated. Repeat MRI and nerve conduction studies remained normal. There was no asterixis or myoclonus, and no cerebellar features. A spinal cord stimulator (SCS) (St Jude Abbott Lamitrode 88 – 1 cm with paddle lead) was inserted at age 67 for refractory symptoms at T11/12 level. She was assessed pre- and post-operatively by measuring independent stance time (Table 1). Balance was objectively measured using a Kistler force platform (9260AA6, Kistler Group, Winterthur, Switzerland) (Supporting Information). This demonstrated a 15 Hz peak on sway analysis concordant with the surface EMG findings. The spinal stimulator was set on bursting mode with burst frequency 40 Hz, intra-burst rate 500 Hz, pulse width 1000 μs, amplitude 0.5 mA. At 1 month follow-up, timed stance with feet apart and eyes open was markedly improved compared with baseline with excellent subjective benefit (Table 1). Repeat surface EMG redemonstrated 15 Hz coherent tremor in standing conditions (Fig. 1A,B). Interestingly, repeat posturography showed abolition of the originally measured 15 Hz peak despite ongoing presence of surface EMG bursting (Fig. 1C). The 15 Hz posturographic peak reappeared within minutes with the spinal stimulator off, observed with repeated testing (Fig. 1D). Posturography at 9 months demonstrated re-emergence of the 15 Hz peak, even with the spinal stimulator on. Follow-up assessments 9 and 13 months post-operatively showed a progressive decline in stance time and increase in subjective unsteadiness, although the latter remained markedly better than pre-operative levels (Table 1). SCS settings remained unchanged due to paresthesia. We demonstrate the abolition of a high frequency spectral peak on posturography in a patient with primary orthostatic tremor during successful treatment with a spinal cord stimulator. Clinical improvement was also seen, in keeping with previous reports.3-6 Interestingly, surface EMG findings remained unchanged. This suggests a potential relationship between posturography and clinical parameters, appearing to be independent of surface EMG findings. Posturography measures ground reaction forces in three axes (anteroposterior, mediolateral, vertical) providing insight into the direction of movement during stance, referred to as sway. The “centre of pressure” (CoP) is a measurement of the location of the vertical force on the surface of a force platform, reflecting the movement of the body required to keep the center of gravity over the base of support.7 The CoP trajectory is then analyzed to assess contributors to balance, and a frequency peak will appear on spectral analysis of the CoP measurements if the sway is concentrated at a particular frequency. Instability in OT is thought to be mediated by an aberrant and highly synchronized central 16 Hz oscillator involved in organizing postural reflexes.8 Disturbance to somatosensory inputs may also play a role; muscle spindles and Golgi tendon organs responsible for proprioceptive information are disrupted by high frequency muscle contractions and patients with OT are considerably more off-balance with eyes closed.9 Interestingly, a 16 Hz peak on posturography is evident in healthy controls when posture is perturbed.8 This may be due to an increased cortical drive to lower limb muscles in the beta band (15–30 Hz), as reported in experimentally induced imbalance in healthy controls.10 The high frequency tremor in OT may also be contributed to by a feeling of subjective unsteadiness. Patients with OT assessed by posturography were shown to have an increasing sense of imbalance during stance, accompanied by increasing EMG activity, suggesting a conscious or subconscious effort to maintain balance.9 In the setting of a coherent high frequency tremor, increasing muscle activity remains tremor-locked, further reinforcing the orthostatic tremor. Subjective unsteadiness was not, however, accompanied by worsening of objective assessments of balance.9 In our patient, clinical parameters improved significantly 1 month post-operatively, coinciding with the abolition of a high frequency peak on posturography. At the 9-month assessment, stance time decreased, and the peak had returned. It is plausible that spinal cord stimulation reduced the sense of subjective imbalance and resulting cortical drive to the muscles to maintain balance, manifesting as abolition of the high frequency posturographic peak. Our findings further support a dissociation between subjective and objective unsteadiness in OT.9 Surface EMG bursting also changed little with therapy, additionally demonstrating a dissociation with subjective unsteadiness. Posturography may be useful as an objective marker of treatment response in primary orthostatic tremor, but this needs confirmation with larger studies. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. S.A.N.: 1B, 3A, 3B T.L.O.: 1C, 3B A.M.: 1C, 3B J.M.: 1B, 1C, 3B N.M.: 1B, 1C, 3B V.S.C.F.: 1A, 1B, 1C, 3A, 3B M.S.: 1A, 1B, 1C, 3A, 3B Ethical Compliance Statement: This work did not require ethics committee approval. The patient provided written consent. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for Previous 12 Months: VSCF receives a salary from NSW Health; has received unrestricted research grants from The Michael J. Fox Foundation; and receives royalties from Health Press, Taylor and Francis Group, and Oxford University Press. NM has received honoraria from AbbVie, Ultrabionics and Medtronic. The remaining authors declare that there are no disclosures. Author disclosures are available in the Supporting Information. The data that support the findings of this study are available from the corresponding author upon reasonable request. Supporting Information The supplementary file contains a detailed description of the posturography protocol, including stance conditions, data acquisition, and analysis methods. Data S1.COI_disclosure. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.