Active clinical trials for "Essential Tremor"

Parkinson's disease and essential tremor are chronic movement disorders for which there is no cure. When medication is no longer effective, deep brain stimulation (DBS) is recommended. Standard DBS is a neuromodulation method that uses a simple monophasic pulse, delivered from an electrode to stimulate neurons in a target brain area. This monophasic pulse spreads out from the electrode creating a broad, electric field that stimulates a large neural population. This can often effectively reduce motor symptoms. However, many DBS patients experience side effects - caused by stimulation of non-target neurons - and suboptimal symptom control - caused by inadequate stimulation of the correct neural target. The ability to carefully manipulate the stimulating electric field to target specific neural subpopulations could solve these problems and improve patient outcomes. The use of complex pulse shapes, specifically biphasic pulses and asymmetric pre-pulses, can control the temporal properties of the stimulation field. Evidence suggests that temporal manipulations of the stimulation field can exploit biophysical differences in neurons to target specific subpopulations. Therefore, our aim is to evaluate the direct neurophysiological effects of complex pulse shapes in DBS movement disorder patients. This will be achieved using a two-stage investigation: stage one will study the neural response to different pulse shapes using electroencephalography (EEG) recordings. Stage two will study the neural responses to different pulse shapes using intra-operative local field potential (LFP) recordings. This study only relates only to the collection of EEG and LFP recordings in DBS patients. The protocol does not cover any surgical procedures, which already take place as part of the patient's normal clinical care.

Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method that works by passing alternating electric current between electrodes where at least one of them is attached to the head. This has been shown to have effects on the motor system, cognition and behavior. The exact mechanism by which tACS causes such effects is not fully understood. Some studies suggests a contribution from the stimulated peripheral nerves present in the scalp rather than direct brain effects. To test this hypothesis two arms will be done. First, 12 subjects (arm 1) will be stimulated using focused 4x1 montage with gel-filled cup-electrodes over the motor cortex and the effects will be compared between anesthetized and non-anesthetized scalp. The effects of anesthetizing the scalp will be tested on three different stimulation amplitudes off (0 mA), low (0.5 mA) and high (2.5 mA). Then, 10 subjects (arm 2) will be stimulated over the contralateral arm to exclude any direct brain stimulation effects and to test if peripheral nerve stimulation can entrain the tremor. Three outcome measurements will be measured during the experiments which are: tremor entrainment, sensation intensity and sensation threshold.

The proposed study is a randomized, single blind trial of intermittent versus continuous stimulation among essential tremor (ET) patients with a chronic history of continuous stimulation.

Essential tremor (ET) is a frequent and disabling disorder with progressive worsening of postural tremor of the upper limbs that impairs most of the manual activities of every day life (feeding, drinking, etc.). Although the pathophysiology of essential tremor (ET) is not fully elucidated, tremor is associated with abnormal activity within different brain regions, in particular the thalamus and the cerebellum. Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM-Thal) reverses the symptoms of tremor but is an invasive procedure. Transcranial stimulation of the cerebellum may represent a non-invasive therapeutic option for ET patients. Here, the investigators propose to test the efficacy of cerebellar stimulation in 15 ET patients previously operated for DBS of the thalamus. To further understand how this treatment provokes tremor reduction, the investigators will analyse the brain neuronal activity in 13 others ET patients candidate to thalamic DBS by using combined electrophysiological recordings of the thalamus (with the electrodes implanted), the cerebellum and the cortex with magnetoencephalography.

This study evaluates the effectiveness of tremor control using various strategies for implementing demand-driven thalamic deep brain stimulation (DBS) for essential tremor. Therapeutic stimulation at the Vim nucleus of the thalamus will be initiated and modulated using signals derived from external sensors (e.g. EMG, accelerometer) and cortical or thalamic electrodes.

The purpose of this investigation is to determine the optimal DRT/VIM target location and its safety margins based on MR-SISET imaging features by comparing with postoperative lesions and clinical outcomes in patients with tremor who will undergo the MRgFUS tremor therapy.

Parkinson's disease and essential tremor are chronic movement disorders for which there is no cure. When medication is no longer effective, deep brain stimulation (DBS) is recommended. Standard DBS is a neuromodulation method that uses a simple monophasic pulse, delivered from an electrode to stimulate neurons in a target brain area. This monophasic pulse spreads out from the electrode creating a broad, electric field that stimulates a large neural population. This can often effectively reduce motor symptoms. However, many DBS patients experience side effects - caused by stimulation of non-target neurons - and suboptimal symptom control - caused by inadequate stimulation of the correct neural target. The ability to carefully manipulate the stimulating electric field to target specific neural subpopulations could solve these problems and improve patient outcomes. The use of complex pulse shapes, specifically biphasic pulses and asymmetric pre-pulses, can control the temporal properties of the stimulation field. Evidence suggests that temporal manipulations of the stimulation field can exploit biophysical differences in neurons to target specific subpopulations. Therefore, our aim is to evaluate the effectiveness of complex pulse shapes to reduce side effects and improve symptom control in DBS movement patients.

The aim of this study is to asses the efficacy and the clinical safety of the transcranial magnetic resonance guided high intensity focused ultrasound system ExAblate 4000, InSightec Ltd. for functional neurosurgery in the treatment of movement disorders. The treatments to be conducted in this study are non-invasive, i.e. without opening the skull, and will create microthalamotomies in specific target areas such as thalamus, subthalamus and pallidum. The data obtained in this study will be used to evaluate the basic safety aspects of this new treatment technology and will serve as a basis for the clinical introduction of MR-guided ultrasound neurosurgery.

Essential Tremor (ET) is the most common tremor disorder, currently affecting an estimated 2.9 million Americans and leading to disability and decreased quality of life in 75% of cases. The pathophysiology of ET is poorly understood, with the source of the tremor remaining controversial since all studies show increased activity in the cerebellum (including mimicked tremor in controls), while animal models of ET using harmaline and a single human PET study implicate the inferior olivary nucleus in the brainstem. There is evidence from the investigator's laboratory that the use of resting-state functional magnetic resonance imaging (rs-fMRI) is useful for characterizing the abnormal tremor neural network in ET compared with controls. The goal is to identify the source of the tremor, which is hypothesized to remain active during rest. Current ET diagnostic criteria require the presence of postural and/or kinetic tremor, which are assumed to be different manifestations of the same tremor oscillator. This long-standing assumption may be incorrect based on several lines of evidence from the investigator's laboratory, and has major implications for understanding ET pathophysiology and treatment. The investigators will test the hypothesis that postural and kinetic tremors are generated through different neural mechanisms. Treatment of ET focuses on pharmacological agents of various mechanisms and rarely deep brain stimulation of the Vim thalamus. Despite the assortment of agents used to treat ET, only ~50% of patients benefit from a particular agent. Furthermore, the mechanisms of action on tremor are not generally known. Understanding the mechanisms of action of various tremor-suppressing agents is critical for future drug development. In this proposal, the investigators plan to study the effects of ethanol (the most efficacious tremor-suppressant currently available) and propranolol (a non-specific β-adrenergic blocker with proven efficacy and unknown mechanism of action) on the tremor neural network.

Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method that works by passing alternating electric current between electrodes where at least one of them is attached to the head. While tACS applied over the motor cortex at the general applied amplitude (1 mA) and using patch electrodes has been shown to entrain physiological tremor in healthy volunteers, the aim of this study is to test the feasibility of using high-amplitude tACS and to assess the effect of different electrode montages and stimulation sites in entraining physiological tremor. First, 10 subjects (arm 1) will be stimulated with 2 mA current amplitude applied between saline soaked patch square electrodes and comparison will be done between motor cortex stimulation and peripheral cortex stimulation. Then, 10 subjects (arm 2) will be stimulated using focused 4x1 montage with gel-filled cup-electrodes and 5 mA amplitude and comparison will be made between motor cortex and occipital cortex stimulation. Three outcome measurements will be measured during the experiments which are: tremor entrainment, phosphene intensity and phosphene threshold.