21 research outputs found
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Non-invasive Brain Stimulation for Essential Tremor
Background: There is increasing interest in the use of non-invasive brain stimulation to characterize and potentially treat essential tremor (ET). Studies have used a variety of stimulation coils, paradigms, and target locations to make these observations. We reviewed the literature to compare prior studies and to evaluate the rationale and the methods used in these studies.
Methods: We performed a systematic literature search of the PubMed database using the terms âtranscranial,â ânoninvasive,â âbrain stimulation,â âtranscranial magnetic stimulation (TMS),â âtranscranial direct current stimulation (tDCS),â âtranscranial alternating current stimulation (tACS),â and âessential tremor.â
Results: Single pulses of TMS to the primary motor cortex have long been known to reset tremor. Although there are relatively few studies showing alterations in motor cortical physiology, such as motor threshold, short and long intracortical inhibition, and cortical silent period, there may be some evidence of altered intracortical facilitation and cerebello-brain inhibition in ET. Repetitive TMS, theta burst stimulation, tDCS, and tACS have been applied to human subjects with tremor with some preliminary signs of tremor reduction, particularly in those studies that employed consecutive daily sessions.
Discussion: A variety of stimulation paradigms and targets have been explored, with the increasing rationale an interest in targeting the cerebellum. Rigorous assessment of coil geometry, stimulation paradigm, rationale for selection of the specific anatomic target, and careful phenotypic and physiologic characterization of the subjects with ET undergoing these interventions may be critical in extending these preliminary findings into effective stimulation therapies
Mapping holmes tremor circuit using the human brain connectome
ObjectiveHolmes tremor is a debilitating movement disorder with limited treatment options. Lesions causing Holmes tremor can occur in multiple different brain locations, leaving the neuroanatomical substrate unclear. Here, we test whether lesion locations that cause Holmes tremor map to a connected brain circuit and whether this circuit might serve as a useful therapeutic target.MethodsCase reports of Holmes tremor caused by focal brain lesions were identified through a systematic literature search. Connectivity between each lesion location and the rest of the brain was computed using resting state functional connectivity magnetic resonance imaging data from 1,000 healthy volunteers. Commonalities across lesion locations were identified. This Holmes tremor circuit was then compared to neurosurgical treatment targets and clinical efficacy.ResultsWe identified 36 lesions causing Holmes tremor, which were scattered across multiple different brain regions. However, all lesion locations were connected to a common brain circuit with nodes in the red nucleus, thalamus, globus pallidus, and cerebellum. In cases with effective neurosurgical treatment, the treatment target was connected with the lesion location, indicating that a second hit to the same circuit might be beneficial. Commonly used deep brain stimulation targets such as the ventral intermediate nucleus and subthalamic nucleus fell outside our Holmes tremor circuit, whereas the globus pallidus target was close, consistent with published clinical response rates for these targets.InterpretationLesions causing Holmes tremor are part of a single connected brain circuit that may serve as an improved therapeutic target.</p
Comparison of VIM and STN DBS for Parkinsonian Resting and Postural/Action Tremor
Background: Resting tremor is common in Parkinsonâs disease (PD), but up to 47% of PD patients have action tremor, which is sometimes resistant to medications. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus or subthalamic nucleus (STN) is effective for medication-refractory tremor in PD, though it remains unclear whether STN DBS is as effective as VIM DBS for postural/action tremor related to PD. Methods: We carried out a single-center retrospective review of patients with medication-refractory resting, postural, and action PD tremor, treated with either VIM or STN DBS between August 2004 and March 2014. We assessed the degree of improvement using items 20 and 21 of the Unified Parkinsonâs Disease Rating Scale (UPDRS) motor scale and examined the proportion of patients achieving tremor arrest. Results: A total of 18 patients were analyzed, 10 treated with STN and eight treated with VIM, with similar off-medication motor UPDRS scores. There was no significant difference in improvement in tremor scores or in the proportion of patients experiencing tremor arrest between the two stimulation sites. Overall, 56% and 72% of patients experienced complete absence of postural/action tremor and resting tremor, respectively, at last follow-up. Discussion This study demonstrated excellent outcomes on both resting and postural/action tremor after either VIM or STN DBS. Resting tremor improved to a greater degree than postural/action tremor in both groups. These results suggest that a large randomized controlled trial is needed to show a superior effect of one target on PD tremor
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A translational approach to capture gait signatures of neurological disorders in mice and humans
A method for capturing gait signatures in neurological conditions that allows comparison of human gait with animal models would be of great value in translational research. However, the velocity dependence of gait parameters and differences between quadruped and biped gait have made this comparison challenging. Here we present an approach that accounts for changes in velocity during walking and allows for translation across species. In mice, we represented spatial and temporal gait parameters as a function of velocity and established regression models that reproducibly capture the signatures of these relationships during walking. In experimental parkinsonism models, regression curves representing these relationships shifted from baseline, implicating changes in gait signatures, but with marked differences between models. Gait parameters in healthy human subjects followed similar strict velocity dependent relationships which were altered in Parkinsonâs patients in ways that resemble some but not all mouse models. This novel approach is suitable to quantify qualitative walking abnormalities related to CNS circuit dysfunction across species, identify appropriate animal models, and it provides important translational opportunities
Perfusion-weighted magnetic resonance imaging thresholds identifying core, irreversibly infarcted tissue.
BACKGROUND AND PURPOSE: Identifying core, irreversibly infarcted tissue and salvageable penumbral tissue is crucial to informed, physiologically guided decision making regarding thrombolytic and other interventional therapies in acute ischemic stroke. Pretreatment perfusion MRI offers promise as a means to differentiate core from penumbral tissues.
METHODS: Diffusion-perfusion MRIs were performed before treatment and on day 7 in patients undergoing successful vessel recanalization with intra-arterial thrombolytic therapy. Perfusion maps of the time to peak of the residue function (Tmax) were generated after deconvolution of an arterial input function. Initial perfusion abnormalities and final infarct regions were outlined by hand. Posttreatment images were coregistered to the pretreatment study. Voxel-by-voxel and volume analyses were performed to identify thresholds of perfusion abnormalities that best predict core, irreversibly infarcted tissue.
RESULTS: Fourteen patients (4 men, 10 women) with vessel recanalization were studied. Mean age was 73 years, and median entry National Institutes of Health Stroke Scale score was 12. Mean time from symptom onset to start of intra-arterial infusion was 245 minutes and to recanalization was 338 minutes. With a voxel-by-voxel analysis, Tmax \u3e or =6 and \u3e or =8 seconds (sensitivity, 71% and 53%; specificity, 63% and 80%) correlated most highly with day 7 final infarct. With a volume analysis, Tmax \u3e or =6 and \u3e or =8 seconds (r2=0.704 and r2=0.705) correlated most highly with day 7 final infarct.
CONCLUSIONS: Perfusion-weighted imaging measures of ischemia severity accurately differentiate irreversibly injured core from penumbral, salvageable tissue. The best threshold for identifying core infarcted tissue is adjusted Tmax of \u3e or =6 to 8 seconds
Perfusion-Weighted Magnetic Resonance Imaging Thresholds Identifying Core, Irreversibly Infarcted Tissue
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A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury
Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9âmg) in patients after acute traumatic cervical SCI. The study enrolled patients 14-75 years of age with acute traumatic cervical SCIs, C4-C7 (motor level) on each side, and American Spinal Injury Association Impairment Scale (AIS) Grade A or B who had spinal decompression/stabilization surgery commencing within 72âh after injury. Patients were randomized 1:1 with stratification by age (<30 vs. â„30 years) and AIS grade (A vs. B with sacral pinprick preservation vs. B without sacral pinprick preservation). A single dose of VX-210 or placebo in fibrin sealant was administered topically onto the dura over the site of injury during decompression/stabilization surgery. Patients were evaluated for medical, neurological, and functional changes, and serum was collected for pharmacokinetics and immunological analyses. Patients were followed up for up to 12 months after treatment. A planned interim efficacy-based futility analysis was conducted after âŒ33% of patients were enrolled. The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI
Design and Feasibility Analysis of a SmartphoneâBased Digital Cognitive Assessment Study in the Framingham Heart Study
Background Smartphoneâbased digital technology is increasingly being recognized as a costâeffective, scalable, and noninvasive method of collecting longitudinal cognitive and behavioral data. Accordingly, a stateâofâtheâart 3âyear longitudinal project focused on collecting multimodal digital data for early detection of cognitive impairment was developed. Methods and Results A smartphone application collected 2 modalities of cognitive data, digital voice and screenâbased behaviors, from the FHS (Framingham Heart Study) multigenerational Generation 2 (Gen 2) and Generation 3 (Gen 3) cohorts. To understand the feasibility of conducting a smartphoneâbased study, participants completed a series of questions about their smartphone and app use, as well as sensory and environmental factors that they encountered while completing the tasks on the app. Baseline data collected to date were from 537 participants (mean age=66.6âyears, SD=7.0; 58.47% female). Across the younger participants from the Gen 3 cohort (n=455; mean age=60.8âyears, SD=8.2; 59.12% female) and older participants from the Gen 2 cohort (n=82; mean age=74.2âyears, SD=5.8; 54.88% female), an average of 76% participants agreed or strongly agreed that they felt confident about using the app, 77% on average agreed or strongly agreed that they were able to use the app on their own, and 81% on average rated the app as easy to use. Conclusions Based on participant ratings, the study findings are promising. At baseline, the majority of participants are able to complete the appârelated tasks, follow the instructions, and encounter minimal barriers to completing the tasks independently. These data provide evidence that designing and collecting smartphone application data in an unsupervised, remote, and naturalistic setting in a large, communityâbased population is feasible