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BACKGROUND - Cervical dystonia is a disabling medical condition that drastically decreases quality of life. Surgical treatment consists of peripheral nerve denervation procedures with or without myectomies or deep brain stimulation (DBS). The current objective was to compare the efficacy of peripheral denervation versus DBS in improving the severity of cervical dystonia through a systematic review and meta-analysis.
METHODS - A search of PubMed, MEDLINE, EMBASE, and Web of Science electronic databases was conducted in accordance with PRISMA guidelines. Preoperative and postoperative Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores were used to generate standardized mean differences and 95% confidence intervals (CIs), which were combined in a random-effects model. Both mean percentage and absolute reduction in TWSTRS scores were calculated. Absolute reduction was used for forest plots.
RESULTS - Eighteen studies met the inclusion criteria, comprising 870 patients with 180 (21%) undergoing DBS and 690 (79%) undergoing peripheral denervation procedures. The mean follow-up time was 31.5 months (range, 12-38 months). In assessing the efficacy of each intervention, forest plots revealed significant absolute reduction in total postoperative TWSTRS scores for both peripheral denervation (standardized mean difference 1.54; 95% CI 1.42-1.66) and DBS (standardized mean difference 2.07; 95% CI 1.43-2.71). On subgroup analysis, DBS therapy was significantly associated with improvement in postoperative TWSTRS severity (standardized mean difference 2.08; 95% CI 1.66-2.50) and disability (standardized mean difference 2.12; 95% CI 1.57-2.68) but not pain (standardized mean difference 1.18; 95% CI 0.80-1.55).
CONCLUSIONS - Both peripheral denervation and DBS are associated with a significant reduction in absolute TWSTRS total score, with no significant difference in the magnitude of reduction observed between the 2 treatments. Further comparative data are needed to better evaluate the long-term results of both interventions.
Copyright © 2018 Elsevier Inc. All rights reserved.
While deep brain stimulation (DBS) treatment is relatively rare in children, it may have a role in dystonia to reduce motor symptoms and disability. Pediatric DBS studies are sparse and limited by small sample size, and thus, outcomes are poorly understood. Thus, we performed a systematic review of the literature including studies of DBS for pediatric (age < 21) dystonia. Patient demographics, disease causes and characteristics, motor scores, and disability scores were recorded at baseline and at last post-operative follow-up. We identified 19 studies reporting DBS outcomes in 76 children with dystonia. Age at surgery was 13.8 ± 3.9 (mean ± SD) years, and 58% of individuals were male. Post-operative follow-up duration was 2.8 ± 2.8 years. Sixty-eight percent of patients had primary dystonia (PD), of whom 56% had a pathological mutation in DYT1 (DYT1+). Across all patients, regardless of dystonia type, 43.8 ± 36% improvement was seen in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor (-M) scores after DBS, while 43.7 ± 31% improvement was observed in BFMDRS disability (-D) scores. Patients with PD were more likely to experience ≥ 50% improvement (56%) in BFMDRS-M scores compared to patients with secondary causes of dystonia (21%, p = 0.004). DYT1+ patients were more likely to achieve ≥ 50% improvement (65%) in BFMDRS-D than DTY1- individuals (29%, p = 0.02), although there was no difference in BFMDRS-M ≥ 50% improvement rates between DYT1+ (66%) or DYT1- (43%) children (p = 0.11). While DBS is less common in pediatric patients, individuals with severe dystonia may receive worthwhile benefit with neuromodulation treatment.
Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.
Focused ultrasound (FUS) has gained recognition as a technique for non-invasive neuromodulation with high spatial precision and the ability to both excite and inhibit neural activity. Here we demonstrate that MRI-guided FUS is capable of exciting precise targets within areas 3a/3b in the monkey brain, causing downstream activations in off-target somatosensory and associated brain regions which are simultaneously detected by functional MRI. The similarity between natural tactile stimulation-and FUS- evoked fMRI activation patterns suggests that FUS likely can excite populations of neurons and produce associated spiking activities that may be subsequently transmitted to other functionally related touch regions. The across-region differences in fMRI signal changes relative to area 3a/3b between tactile and FUS conditions also indicate that FUS modulated the tactile network differently. The significantly faster rising (>1 sec) fMRI signals elicited by direct FUS stimulation at the targeted cortical region suggest that a different neural hemodynamic coupling mechanism may be involved in generating fMRI signals. This is the first demonstration of imaging neural excitation effects of FUS with BOLD fMRI on a specific functional circuit in non-human primates.
Frontal-basal ganglia circuitry dysfunction caused by Parkinson's disease impairs important executive cognitive processes, such as the ability to inhibit impulsive action tendencies. Subthalamic Nucleus Deep Brain Stimulation in Parkinson's disease improves the reactive inhibition of impulsive actions that interfere with goal-directed behavior. An unresolved question is whether this effect depends on stimulation of a particular Subthalamic Nucleus subregion. The current study aimed to 1) replicate previous findings and additionally investigate the effect of chronic versus acute Subthalamic Nucleus stimulation on inhibitory control in Parkinson's disease patients off dopaminergic medication 2) test whether stimulating Subthalamic Nucleus subregions differentially modulate proactive response control and the proficiency of reactive inhibitory control. In the first experiment, twelve Parkinson's disease patients completed three sessions of the Simon task, Off Deep brain stimulation and medication, on acute Deep Brain Stimulation and on chronic Deep Brain Stimulation. Experiment 2 consisted of 11 Parkinson's disease patients with Subthalamic Nucleus Deep Brain Stimulation (off medication) who completed two testing sessions involving of a Simon task either with stimulation of the dorsal or the ventral contact in the Subthalamic Nucleus. Our findings show that Deep Brain Stimulation improves reactive inhibitory control, regardless of medication and regardless of whether it concerns chronic or acute Subthalamic Nucleus stimulation. More importantly, selective stimulation of dorsal and ventral subregions of the Subthalamic Nucleus indicates that especially the dorsal Subthalamic Nucleus circuitries are crucial for modulating the reactive inhibitory control of motor actions.
Copyright © 2017 Elsevier Ltd. All rights reserved.
BACKGROUND - Thalamic size and shape vary significantly across patients - with changes specific to the anterior thalamus occurring with age and in the setting of chronic epilepsy. Such ambiguity raises concerns regarding electrode position and potential implications for seizure outcomes.
METHODS - MRIs from 6 patients from a single center underwent quantitative analysis. In addition to direct measurements from postimplantation MRIs, the CRAnialVault Explorer suite was used to normalize electrode position to a common reference system. Relationships between thalamic dimensions, electrode location, and seizure outcome were analyzed.
RESULTS - Although this study group was too small to sufficiently power statistical analysis, general trends were identified. There was a trend towards smaller thalamic volumes in nonresponders. Electrode locations demonstrated more variation after normalization. There was a trend towards a more lateral, posterior, and inferior electrode position in nonresponders.
CONCLUSIONS - Variations in thalamic shape and volume necessitate direct targeting. Given that changes occur to thalamic anatomy with age and in the setting of epilepsy, improved methods for visualizing and targeting the anterior nucleus are necessary. Pronounced thalamic atrophy may preclude proper electrode placement and serve as a poor prognostic indicator. A greater understanding of thalamic anatomy and connectivity is necessary to optimize deep brain stimulation for epilepsy.
© 2016 S. Karger AG, Basel.
INTRODUCTION - Deep brain stimulation (DBS) is an established therapy for movement disorders, and is under active investigation for other neurologic and psychiatric indications. While many studies describe outcomes and complications related to stimulation therapies, the majority of these are from large academic centers, and results may differ from those in general neurosurgical practice.
METHODS - Using data from both the Centers for Medicare and Medicaid Services (CMS) and the National Surgical Quality Improvement Program (NSQIP), we identified all DBS procedures related to primary placement, revision, or removal of intracranial electrodes. Cases of cortical stimulation and stimulation for epilepsy were excluded.
RESULTS - Over 28,000 cases of DBS electrode placement, revision, and removal were identified during the years 2004-2013. In the Medicare dataset, 15.2% and of these procedures were for intracranial electrode revision or removal, compared to 34.0% in the NSQIP dataset. In NSQIP, significant predictors of revision and removal were decreased age (odds ratio (OR) of 0.96; 95% CI: 0.94, 0.98) and higher ASA classification (OR 2.41; 95% CI: 1.22, 4.75). Up to 48.5% of revisions may have been due to improper targeting or lack of therapeutic effect.
CONCLUSION - Data from multiple North American databases suggest that intracranial neurostimulation therapies have a rate of revision and removal higher than previously reported, between 15.2 and 34.0%. While there are many limitations to registry-based studies, there is a clear need to better track and understand the true prevalence and nature of such failures as they occur in the wider surgical community.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for ameliorating the motor symptoms of Parkinson's disease (PD) including bradykinesia. The STN receives its main excitatory input from cortex; however, the contribution of cortico-subthalamic projection neurons to the effects of DBS remains unclear. To isolate the consequences of stimulating layer 5 primary motor cortex (M1) projections to the STN, we used a dual virus transfection technique to selectively express opsins in these neurons in mice made parkinsonian by unilateral nigrostriatal 6-OHDA lesioning. AAVs containing WGA-Cre constructs were injected in the STN to retrogradely place Cre in STN afferents, while AAVs containing Cre-dependent ultrafast hChR2(E123T/T159C)-EYFP opsin constructs were injected in M1 layer 5, producing specific opsin expression in M1-STN projections. Under unstimulated conditions, lesioned mice showed bradykinesia and hypokinesia (decreased movement), along with electrophysiological changes similar to those observed in PD patients. Specifically, low frequency power (theta, alpha, low beta) was increased and gamma power was decreased, while M1/STN coherence and STN phase-amplitude-coupling (PAC) were increased. Optogenetic stimulation (100-130Hz) of STN afferents in these mice ameliorated bradykinesia and hypokinesia and brought the neural dynamics closer to the non-parkinsonian state by reducing theta and alpha and increasing gamma power in M1, decreasing STN PAC, and reducing theta band coherence. Histological examination of the EYFP expression revealed that, in addition to orthodromic and antidromic effects, stimulation of cortico-subthalamic neurons may cause wide-spread increased glutamatergic activity due to collaterals that project to areas of the thalamus and other brain regions.
Copyright © 2016 Elsevier Inc. All rights reserved.
BACKGROUND AND IMPORTANCE - The ventral intermediate nucleus of the thalamus is a primary target of deep brain stimulation (DBS) in patients with essential tremor. Despite reliable control of contralateral tremor, there is sometimes a need for lead revision in cases of infection, hardware malfunction, or failure to relieve symptoms. Here, we present the case of a patient undergoing revision after ventral intermediate nucleus (Vim) DBS failed to control his tremor. During the electrode removal, the distal portion of the lead was found to be tightly adherent to tissue within the deep brain. Partial removal of the electrode in turn caused weakness, paresthesias, and tremor control similar to the effects produced by thalamotomy or thalamic injury.
CLINICAL PRESENTATION - A 48-year-old man with essential tremor had bilateral Vim DBS leads implanted 10 years earlier but had poor control of his tremor and ultimately opted for surgical revision with lead placement in the zona incerta. During attempted removal of his right lead, the patient became somnolent with contralateral weakness and paresthesias. The procedure was aborted, and postoperative neuroimaging was immediately obtained, showing no signs of stroke or hemorrhage. The patient had almost complete control of his left arm tremor postoperatively, and his weakness soon resolved.
CONCLUSION - To the best of our knowledge, this is the first reported case of cerebral injury after DBS revision and offers insights into the mechanism of high-frequency electric stimulation compared with lesions. That is, although high-frequency stimulation failed to control this patient's tremor, thalamotomy-like injury was completely effective.
Surgery can be a highly effective treatment for medically refractory temporal lobe epilepsy (TLE). The emergence of minimally invasive resective and nonresective treatment options has led to interest in epilepsy surgery among patients and providers. Nevertheless, not all procedures are appropriate for all patients, and it is critical to consider seizure outcomes with each of these approaches, as seizure freedom is the greatest predictor of patient quality of life. Standard anterior temporal lobectomy (ATL) remains the gold standard in the treatment of TLE, with seizure freedom resulting in 60-80% of patients. It is currently the only resective epilepsy surgery supported by randomized controlled trials and offers the best protection against lateral temporal seizure onset. Selective amygdalohippocampectomy techniques preserve the lateral cortex and temporal stem to varying degrees and can result in favorable rates of seizure freedom but the risk of recurrent seizures appears slightly greater than with ATL, and it is not clear whether neuropsychological outcomes are improved with selective approaches. Stereotactic radiosurgery presents an opportunity to avoid surgery altogether, with seizure outcomes now under investigation. Stereotactic laser thermo-ablation allows destruction of the mesial temporal structures with low complication rates and minimal recovery time, and outcomes are also under study. Finally, while neuromodulatory devices such as responsive neurostimulation, vagus nerve stimulation, and deep brain stimulation have a role in the treatment of certain patients, these remain palliative procedures for those who are not candidates for resection or ablation, as complete seizure freedom rates are low. Further development and investigation of both established and novel strategies for the surgical treatment of TLE will be critical moving forward, given the significant burden of this disease.
Copyright © 2015 Elsevier Inc. All rights reserved.