Habituation After Deep Brain Stimulation in Tremor Syndromes: Prevalence, Risk Factors and Long-Term Outcomes

Deep brain stimulation (DBS) of the thalamus is an effective treatment for medically refractory essential, dystonic and Parkinson's tremor. It may also provide benefit in less common tremor syndromes including, post-traumatic, cerebellar, Holmes, neuropathic and orthostatic tremor. The long-term benefit of DBS in essential and dystonic tremor (ET/DT) often wanes over time, a phenomena referred to as stimulation “tolerance” or “habituation”. While habituation is generally accepted to exist, it remains controversial. Attempts to quantify habituation have revealed conflicting reports. Placebo effects, loss of micro-lesional effect, disease related progression, suboptimal stimulation and stimulation related side-effects may all contribute to the loss of sustained long-term therapeutic effect. Habituation often presents as substantial loss of initial DBS benefit occurring as early as a few months after initial stimulation; a complex and feared issue when faced in the setting of optimal electrode placement. Simply increasing stimulation current tends only to propagate tremor severity and induce stimulation related side effects. The report by Paschen and colleagues of worsening tremor scores in the “On” vs. “Off” stimulation state over time, even after accounting for “rebound” tremor, supports the concept of habituation. However, these findings have not been consistent across all studies. Chronic high intensity stimulation has been hypothesized to induce detrimental plastic effects on tremor networks, with some lines of evidence that DT and ET may be more susceptible than Parkinson's tremor to habituation. However, Tsuboi and colleague's recent longitudinal follow-up in dystonic and “pure” essential tremor suggests otherwise. Alternatively, post-mortem findings support a biological adaption to stimulation. The prevalence and etiology of habituation is still not fully understood and management remains difficult. A recent study reported that alternating thalamic stimulation parameters at weekly intervals provided improved stability of tremor control consistent with reduced habituation. In this article the available evidence for habituation after DBS for tremor syndromes is reviewed; including its prevalence, time-course, possible mechanisms; along with expected long-term outcomes for tremor and factors that may assist in predicting, preventing and managing habituation.

Radiosurgical treatment of medically refractory Parkinson’s tremor

Introduction. In spite of medication treatment being today the basic form of treatment for Parkinson’s disease, surgical methods may be preferable to improve symptoms of the disease. Radiosurgery is one of them, but in Russia, to date, there are no publications summarizing data about the experience of using this method throughout the country.The study objective is to evaluate the effect of radiosurgical thalamotomy (destruction of the intermediate ventral nucleus of the thalamus) on the severity of tremor in patients with Parkinson’s disease, as well as to estimate the frequency of complications of this intervention, the frequency of different variants of radiological and clinical-neurological response.Materials and methods. One hundred and one (101) patients with medically refractory Parkinson’s tremor received Gamma Knife radiosurgery in our centre over a 10‑year period, of whom 10 patients were treated bilaterally. Pre-treatment evaluation was done using tremor assessment scales and video recordings of tremor intensity. Gamma Knife radiosurgery was provided with Leksell Gamma Knife 4C and Leksell Gamma Knife Perfexion (Elekta AB, Sweden) preceded by magnetic resonance tractography the day before treatment. The same planning protocol was used for all patients, the target was ventral intermediate nucleus and the prescription dose of 130 Gy was delivered with a 4 mm isocenter. After treatment, patients were evaluated radiologically and neurologically at regular 6‑month intervals, as well as through telephone interviews and video recordings.Results. Ninety-two (92) patients were included in the analysis of the results of radiosurgical treatment. Median follow-up time after radiosurgery was 26 months, from 6 to 113 months. Tremor reduction was achieved in 76 % of the patients, 61 % of whom had almost complete tremor arrest. Decreased tremors were observed from 1 to 6 months after treatment, with a mean of 4 months. Three (3) patients experienced tremor resurgence after 3–7 years. Complications were observed in 6.5 % of patients and were transient in character. Some of the patients developed severe depression. Only 1 patient had a serious complication in the form of thalamic haemorrhage (at 22 months after treatment). Ten (10) patients who were treated bilaterally all showed considerable clinical improvement and absence of complications.Conclusion. Gamma Knife radiosurgery is a safe and effective functional neurosurgical procedure for tremor correction to improve patients’ quality of life, especially when deep brain stimulation is not accessible. Patients with severe medically refractory tremors are good candidates for Gamma Knife treatment, which showed high efficacy and a low risk of complications.

A Study on the Essential and Parkinson’s Arm Tremor Classification

In this article, the challenge of discriminating between essential and Parkinson’s tremor is addressed. Although a variety of methods have been proposed for diagnosing the severity of these highly occurring tremor types, their rapid and effective identification, especially in their early stages, proves particularly difficult and complicated due to their wide range of causes and similarity of symptoms. To this goal, a clinical analysis was performed, where a number of volunteers including essential and Parkinson’s tremor-diagnosed patients underwent a series of pre-defined motion patterns, during which a wearable sensing setup was used to measure their lower arm tremor characteristics from multiple selected points. Extracted features from the acquired accelerometer signals were used to train classification algorithms, including decision trees, discriminant analysis, support vector machine (SVM), K-nearest neighbor (KNN) and ensemble learning algorithms, for providing a comparative study and evaluating the potential of utilizing machine learning to accurately discriminate among different tremor types. Overall, SVM related classifiers proved to be the most successful in terms of classifying between Parkinson’s, essential and no tremor diagnosed with percentages reaching up to 100% for a single accelerometer measurement at the metacarpal area. In general and in motion while holding an object position, Coarse Gaussian SVM classifier reached 82.62% accuracy.

Subthalamic-Cortical Network Reorganization during Parkinson’s Tremor

ABSTRACTTremor, a common and often primary symptom of Parkinson’s disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from ten patients performing a naturalistic visual-motor task. From this task we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state.SIGNIFICANCE STATEMENTTremor is a common symptom of Parkinson’s disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello-thalamic-cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this manuscript, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation (DBS) surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson’s tremor, while describing the short-timescale dynamics of subcortical-cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.