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Gait Ataxia in Essential Tremor Modulated by Thalamic Deep Brain Stimulation
Abstract & Commentary
By Jordan Dubow, MD, and Claire Henchcliffe, MD, DPhil. Dr. Dubow is Vascular Neurology Fellow, Weill Cornell Medical College. Dr. Henchcliffe is Associate Professor of Neurology and Neuroscience, Weill Cornell Medical Center. Dr. Dubow reports no financial relationships relevant to this field of study, Dr. Henchcliffe reports she is on the speaker's bureau and advisory board for Allergan and Teva; speaker's bureau for Boehringer-Ingelheim, GlaxoSmithKline, and Novartis; advisory board for Merz, and is a consultant for Gerson Lehman Group and Guidepoint Global.
Synopsis: Thalamic deep brain stimulation improves ataxia in subjects with essential tremor at therapeutic stimulation parameters, and worsens ataxia at supra-therapeutic parameters.
Source: Fasano A, Herzog J, Raethjen, J et al. Gait ataxia in essential tremor is differentially modulated by thalamic stimulation. Brain 2010;133:3635-3648.
Essential tremor (ET) is the most common form of pathological tremor. However, older patients with ET and those with more than five years of disease duration have abnormalities of gait as well as limb ataxia. Tremor refractory to medication typically responds exquisitely to deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM), but DBS effects on ataxia remain to be characterized.
In the present study, 11 patients with ET (age 69.8 ± 3.9 years, disease duration 24.4 ± 11.2 years) were evaluated 24.7 ± 20.3 months after bilateral thalamic DBS and compared to 10 age- and gender-matched healthy controls. Tremor was assessed with a modified version of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). Ataxia was rated using the International Cooperative Ataxia Rating Scale (ICARS), a 100-point scale that quantifies ataxia in four categories of movement, with higher scores indicating worsened ataxia. Normal gait speed and tandem gait speed were measured, and gait analysis was also performed on a motor-driven treadmill, recorded with an infrared movement analysis system. To quantify ataxia of gait, an ataxia ratio was computed, and coefficients of variation of gait cycle time and swing phase duration were calculated. Assessments were performed in ET subjects during three stimulation conditions: "stimulation ON," "stimulation OFF," and supra-therapeutic stimulation.
Thalamic DBS resulted in a 66% reduction of the TRS score under "stimulation ON" compared to the "stimulation OFF" conditions. Supra-therapeutic stimulation also reduced tremor severity, but worsened spiral drawing due to stimulation-induced ataxia. The ICARS score was significantly higher in the "stimulation OFF" compared to the "stimulation ON" state, and "stimulation ON" also significantly reduced the number of missteps compared to "stimulation OFF" and supra-therapeutic stimulation. Velocity of tandem gait was significantly faster in the "stimulation ON" compared to the supra-therapeutic stimulation, and velocity of routine walking was significantly faster in the "stimulation ON" compared to "stimulation OFF" and supra-therapeutic stimulation.
On treadmill gait analysis, the foot trajectories of patients with essential tremor were highly variable (ataxic) during "stimulation OFF." During "stimulation ON," foot trajectories improved and were indistinguishable from controls in some patients. During "stimulation ON," the ataxia ratio and the coefficient of variation during swing phase were significantly lower than during "stimulation OFF" and supra-therapeutic stimulation. The ataxia ratio and the coefficient of variation of swing phase were significantly higher during "stimulation OFF" and supra-therapeutic stimulation compared to "stimulation ON."
This study confirms that essential tremor, now felt to be a neurodegenerative condition, is not a monosymptomatic disorderadvanced patients may develop a cerebellar disorder with both midline and hemispheric cerebellar signs compared to healthy controls. The fact that thalamic stimulation improved cerebellar symptoms at therapeutic parameters, and worsened ataxia at supra-therapeutic stimulation parameters, offers insight into both clinical treatment of ataxia and to the anatomical localization of ataxia in ET. Critically, this study raises the question of whether DBS of the VIM nucleus of the thalamus may be beneficial for patients with other causes of ataxia, such as multiple system atrophy or the spinocerebellar ataxias. One strength of the study lies in its careful, precise, and objective motor evaluations, but none of the study subjects had ataxia that interfered with their walking or day-to-day function, and improvements were seen only on scales and not with functional assessment. Therefore, we do not know if thalamic DBS would indeed provide meaningful impact in patients with much more severe ataxia. Further study is certainly warranted, and this is underlined by Earhart and colleagues.1 who reported that DBS effects upon gait and balance are highly variable in individuals with ET. Finally, another observation of this study was that patients with essential tremor had slower gaits in routine walking compared to controls. Some individuals with ET progress to Parkinson's disease, and it would be fascinating to determine whether motor measures used in this study could be early predictors of later ET subtypes.
1. Earhart GM, Clark BR, Tabbal SD, Perlmutter JS. Gait and balance in essential tremor: Variable effects of bilateral thalamic stimulation. Mov Disord 2009;24:386-391.