The nature of tremor circuits in parkinsonian and essential tremor (original) (raw)
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Deep Brain Stimulation Target Selection in Co-Morbid Essential Tremor and Parkinson’s Disease
Tremor and Other Hyperkinetic Movements, 2020
A 64-year-old right-handed male with essential tremor (ET) since the age of 18 presented for management of debilitating bilateral upper extremity action tremor. As a result, he had difficulty using his hands for eating, buttoning his clothes, and shaving. One year before presentation, he had also developed left lower extremity resting tremor. He had failed propranolol due to a lack of efficacy and could not tolerate primidone due to adverse effects. In addition to bilateral upper extremity action tremor (see Figure 1 for spiral drawing), examination showed rest tremor in both upper and lower extremities, chin tremor, hypomimia, hypometric saccadic eye movements, along with reduced arm swing and stride length when walking. Bradykinesia was present bilaterally but could not be accurately quantified due to severe overlying tremor. A clinical diagnosis of ET and Parkinson's disease (PD) was made, based on the long-standing history of action tremor with onset in the upper extremities (ET), and more recent development of asymmetric rest tremor, bradykinesia and hypomimia (PD) [1]. A trial of a low dose of carbidopa-levodopa did not offer many benefits and was subsequently discontinued per patient preference. He was thus referred for deep brain stimulation (DBS) to address refractory tremor. Clinical Dilemma DBS is recommended for PD patients with medically refractory tremor or motor fluctuations. Studies have shown comparable improvement in motor symptoms with stimulation
Experimental Neurology, 2012
Different tremor entities such as Essential Tremor (ET) or tremor in Parkinson's disease (PD) can be ameliorated by the implantation of electrodes in the ventral thalamus for Deep Brain Stimulation (DBS). The exact neural mechanisms underlying this treatment, as well as the specific pathophysiology of the tremor in both diseases to date remain elusive. Since tremor-related local field potentials (LFP) have been shown to cluster with a somatotopic representation in the subthalamic nucleus, we here investigated the neurophysiological correlates of tremor in the ventral thalamus in ET and PD using power and coherence analysis. Local field potentials (LFPs) at different recording depths and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm were recorded simultaneously in twelve ET and five PD patients. Data analysis revealed individual electrophysiological patterns of LFP-EMG coherence at single and double tremor frequency for each patient. Patterns observed varied in their spatial distribution within the Ventral lateral posterior nucleus of the thalamus (VLp), revealing a specific topography of 'tremor clusters' for PD and ET. The data strongly suggest that within VLp individual tremor-related electrophysiological signatures exist in ET and PD tremor.
Modulation of tremor amplitude during deep brain stimulation at different frequencies
Brain and Cognition, 2003
Rest tremor was quantified in the index finger tip of 16 patients with ParkinsonÕs disease (PD) receiving deep brain stimulation (DBS) of the ventro-intermediate nucleus (Vim) of the thalamus, the subthalamic nucleus (STN), or the internal part of the globus pallidus (GPi) while being off L L -dopa for 12 h. Clinically, without DBS, tremor amplitude varied from absent to high. Tremor was recorded continuously for about 5 min under three conditions of DBS repeated twice, namely, effective frequency (E), ineffective frequency (I), and no DBS (O). No changes in tremor were observed across conditions in subjects with little or no tremor. However, in subjects with moderate to large amplitude tremor, DBS decreased tremor amplitude to near normal values within a few seconds. Generally, transitions were progressive and occurred with a varying time delay. Occasionally, tremor escaped from control regardless of the stimulation condition considered. In some cases tremor amplitude in one condition appeared to depend on the preceding condition. Finally, the results were reproducible on two consecutive days. We conclude that tremor control with DBS follows specific dynamical rules, which must be compatible with the hypotheses proposed regarding the underlying mechanisms of DBS.
Deep brain stimulation and medication for parkinsonian tremor during secondary tasks
Movement Disorders, 2007
This study examined the efficacy of subthalamic nucleus (STN), deep brain stimulation (DBS), and medication for resting tremor during performance of secondary tasks. Hand tremor was recorded using accelerometry and electromyography (EMG) from 10 patients with Parkinson's disease (PD) and ten matched control subjects. The PD subjects were examined off treatment, on STN DBS, on medication, and on STN DBS plus medication. In the first experiment, tremor was recorded in a quiet condition and during a cognitive task designed to enhance tremor. In the second experiment, tremor was recorded in a quiet condition and during isometric finger flexion (motor task) with the contralateral limb at 5% of the maximal voluntary contraction (MVC) that was designed to suppress tremor. Results showed that: (1) STN DBS and medication reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS normalized tremor frequency in both the quiet and cognitive task conditions, whereas tremor amplitude was only normalized in the quiet condition, (3) a secondary motor task reduced tremor in a similar manner to STN DBS. These findings demonstrate that STN DBS still suppresses tremor in the presence of a cognitive task. Furthermore, a secondary motor task of the opposite limb suppresses tremor to levels comparable to STN DBS.
Thalamic deep brain stimulation for tremor-predominant Parkinson's disease
Parkinsonism & Related Disorders, 2003
Objectives. Determine the long-term efficacy of thalamic deep brain stimulation (DBS) for treatment of tremor among individuals with tremor-predominant Parkinson's disease (PD). Design. Longitudinal, unblinded assessment of tremor and activities of daily living (ADL) at baseline (pre-surgical), and post-operative intervals of 1, 3, and 12 months, and annually thereafter up to 3 years. Methods. A clinical series of 19 individuals undergoing placement of a DBS system for treatment of PD-related tremor. A battery of subjective and objective measures of tremor was completed at planned pre-and post-operative intervals. Results. Stimulation was associated with significant improvement on subjective and objective measures of ADL performance, midline tremor, and contralateral upper and lower extremity tremor, including parkinsonian resting and action tremors, over the follow-up period. Ipsilateral tremor showed little or no effect of stimulation after the first 3 months. Antiparkinsonian medication use and stimulation parameters showed little or no change over the course of follow-up. About half (53%) of all individuals reported at least one side effect, generally mild, during the follow-up period, with paresthesias and dysarthria being the most common. A total of two leads required replacement due to (1) infection, and (2) adverse side effects (i.e. burning and tingling with stimulation). Conclusion. DBS is associated with stable tremor control in PD. Side-effects are typically easily managed with stimulation adjustments, although in some cases lead replacement may be required.
Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor
Essential tremor is the most prevalent movement disorder and is often refractory to medical treatment. Deep brain stimulation (DBS) offers a therapeutic approach that can efficiently control tremor symptoms. Several DBS targets (ventral intermediate nucleus, zona incerta, posterior subthalamic area) have been discussed for tremor treatment. Effective DBS therapy for tremor critically involves optimal targeting to modulate the tremor network. This could potentially become more robust and precise by using state-of-the-art brain connectivity measurements. In the current study, we utilized two normative brain connectomes (structural and functional) to show the pattern of effective DBS electrode connectivity in 33 essential tremor patients. Our structural and functional connectivity models were significantly predictive of post-operative tremor improvement in out-of-sample data (structural, R = 0.48, p < 10-4; functional, R < 0.41, p = 0.001; leave-one-out cross-validation). Additio...
Thalamic Deep Brain Stimulation in Essential Tremor Plus Is as Effective as in Essential Tremor
Brain Sciences
The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn–Tolosa–Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show tha...
Journal of Neurosurgery, 2000
MPROVED understanding of the pathophysiological basis of movement disorders, as well as improved neurosurgical techniques, have led to a resurgence in stereotactic interventions for the treatment of motor impairments in PD and other movement disorders. 2,15 For example, chronic DBS directed to thalamic nuclei has been used for several decades to treat parkinsonian tremor, essential tremor, and other tremors. The clinical efficacy of DBS has improved with the progressive refinement of this intervention, which has several advantages over thalamotomy (for example, reversibility and modulation of DBS over time). 12,15 However, despite the fact that the neuroanatomical locus of the DBS electrodes is a critical determinant of therapy efficacy, there is little information correlating the clinical efficacy of DBS in patients with essential tremor with the location of the stimulating electrodes in the brain postmortem. For this reason, we report neuropathological postmortem studies of the brain in a woman in whom essential tremor was suppressed by bilateral thalamic DBS. These studies show that both stim-ulating electrodes terminated in the region of the thalamic Vim and that chronic DBS induced only minor reactive changes that were confined to the electrode tracks.
Distinguishing the Central Drive to Tremor in Parkinson's Disease and Essential Tremor
Journal of Neuroscience, 2015
Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N ϭ 24) and ET (N ϭ 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology.
Neuroimage, 2004
We used 15 O-labeled water (H 2 15 O) positron emission tomography (PET) to study eight Parkinson's disease (PD) patients with unilateral ventral intermediate (Vim) thalamic nucleus deep brain stimulation (DBS) for severe tremor. Triaxial accelerometry (TRIAX) was used during imaging to obtain on-line measures of tremor characteristics. Regional cerebral blood flow (rCBF) scans together with TRIAX recordings were collected in three stimulation conditions (OFF, MID, and ON, corresponding, respectively, to 0%, 50%, and 100% reductions in mean accelerometry signal). Statistical Parametric Mapping (SPM99) revealed significant rCBF reductions during stimulation in the ipsilateral sensorimotor cortex (SMC) and the contralateral cerebellum, as well as concurrent increases in the ipsilateral ventral thalamus ( P < 0.05, corrected). Covariate analysis of rCBF with physiological tremor characteristics revealed that tremor acceleration correlated positively with changes in the SMC and supplementary motor cortex ipsilaterally ( P < 0.05, uncorrected), and negatively with changes in the ipsilateral cuneus ( P < 0.05, corrected). After removing tremor acceleration effects, changes in tremor frequency correlated negatively with changes in the contralateral dentate nucleus and pons ( P < 0.05, uncorrected). Our results suggest that Vim DBS for PD tremor modulates the activity of cerebello-thalamo-cortical pathways. Specific tremor characteristics relate to activity in different nodes of this system. D