Effect of Dexmedetomidine on Perception of Paresthesia during Subthalamic Nucleus Deep Brain Stimulation Surgery for Parkinson's Disease.

Background: Deep brain stimulation (DBS) has become a well-established treatment for the management of Parkinson's disease (PD). The most common method of lead targeting utilizes microelectrode recording (MER) and intraoperative macrostimulation to confirm accurate placement of the lead. This has been significantly aided by the use of dexmedetomidine (DEX) sedation during the procedure. Despite the frequent use of DEX, it has been theorized that DEX may have some effects on the MER during intraoperative testing. The effect on the perception of sensory thresholds during macrostimulation in the form of paresthesia is still unreported. Objectives: To investigate the effect of the sedative DEX on sensory perception thresholds observed in the intraoperative versus postoperative settings for patients undergoing subthalamic nucleus (STN) DBS surgery for PD. Materials and Methods: Adult patients (n = 8) with a diagnosis of PD underwent placement of DBS leads (n = 14) in the STN. Patients were subjected to intraoperative macrostimulation for capsular and sensory thresholds prior to placement of each DBS lead. These were compared to sensory thresholds observed in the postoperative setting during outpatient programming at three depths on each lead (n = 42). Results: In most contacts (22/42) (P = 0.19), sensory thresholds for paresthesia perception were either perceived at a higher voltage or absent during intraoperative testing in comparison to those observed in the postoperative setting. Conclusions: DEX appears to have measurable (though not statistically significant) effect on the perception of paresthesia observed during intraoperative testing.

A Case Report of Siblings with Dystonia: A Potential Link Between DYT11 Mutation and Platelet Dysfunction.

Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder due to a mutated epsilon-sarcoglycan gene (SGCE) at the dystonia 11 (DYT11) locus on chromosome 7q21-31. ε-sarcoglycan has been identified in vascular smooth muscle and has been suggested to stabilize the capillary system. This report describes two siblings with MDS treated with bilateral globus pallidus interna deep brain stimulation. One patient had a history of bleeding following dental procedures, menorrhagia, and DBS placement complicated by intraoperative bleeding during cannula insertion. The other sibling endorsed frequent epistaxis. Subsequent procedures were typically treated perioperatively with platelet or tranexamic acid transfusion. Hematologic workup showed chronic borderline thrombocytopenia but did not elucidate a cause-specific platelet dysfunction or underlying coagulopathy. The bleeding history and thrombocytopenia observed suggest a potential link between MDS and platelet dysfunction. Mutated ε-sarcoglycan may destabilize the capillary system, thus impairing vasoconstriction and leading to suboptimal platelet aggregation.

Enhancing analgesic spinal cord stimulation for chronic pain with personalized immersive virtual reality.

ABSTRACT: Spinal cord stimulation (SCS) is an approved treatment for truncal and limb neuropathic pain. However, pain relief is often suboptimal and SCS efficacy may reduce over time, requiring sometimes the addition of other pain therapies, stimulator revision, or even explantation. We designed and tested a new procedure by combining SCS with immersive virtual reality (VR) to enable analgesia in patients with chronic leg pain. We coupled SCS and VR by linking SCS-induced paresthesia with personalized visual bodily feedback that was provided by VR and matched to the spatiotemporal patterns of SCS-induced paresthesia. In this cross-sectional prospective interventional study, 15 patients with severe chronic pain and an SCS implant underwent congruent SCS-VR (personalized visual feedback of the perceived SCS-induced paresthesia displayed on the patient's virtual body) and 2 control conditions (incongruent SCS-VR and VR alone). We demonstrate the efficacy of neuromodulation-enhanced VR for the treatment of chronic pain by showing that congruent SCS-VR reduced pain ratings on average by 44%. Spinal cord stimulation-VR analgesia was stronger than that in both control conditions (enabling stronger analgesic effects than incongruent SCS-VR analgesia or VR alone) and kept increasing over successive stimulations, revealing the selectivity and consistency of the observed effects. We also show that analgesia persists after congruent SCS-VR had stopped, indicating carry over effects and underlining its therapeutic potential. Linking latest VR technology with recent insights from the neuroscience of body perception and SCS neuromodulation, our personalized new SCS-VR platform highlights the impact of immersive digiceutical therapies for chronic pain.Registration: clinicaltrials.gov, Identifier: NCT02970006.

Fundamentals of Neuromodulation and Pathophysiology of Neural Networks in Health and Disease.

Neuromodulation involves altering neuronal circuitry and subsequent physiological changes with the aim to ameliorate neurological symptoms. Over the years several techniques have been used to obtain neuromodulatory effects for treatment of conditions including Parkinson disease, essential tremor, dystonia or seizures. We provide brief description of the various therapeutics that have been used and mechanisms involved in pathophysiology of these disorders as well as the therapeutic mechanisms of the treatment modalities.

Microsurgery and Neuromodulation for Facial Spasms.

Facial spasms are of various types. Hemifacial spasm (HFS) is characterized by unilateral tonic-clonic contractions of facial muscles, following a specific pattern of disease progression. It has well-delineated clinical, radiological and electrophysiological features. We have conducted an extensive review of existing literature on the subject, as regards etiopathogenesis, clinical features, investigations and management options for facial spasms. Primary Hemifacial spasm (HFS) may be treated using pharmacotherapy, botulinum toxin injections or microvascular decompression surgery. Microvascular decompression has the potential to reverse the pathological changes of the disease and has proved to be the most successful of all treatment options. Other facial spasms are exceedingly difficult to treat and may need neuromodulation as an option. The following article attempts to review the clinical features and therapeutic approaches to managing patients with facial spasms.

Neuromodulation Options and Patient Selection for Parkinson's Disease.

Neuromodulation therapies, including deep brain stimulation (DBS) and pump therapies, are currently the standard of care for PD patients with advanced disease and motor complications that are difficult to control with medical management alone. The quest for alternate lesser invasive approaches led to the development of several novel therapies like intrajejunal levodopa infusions (IJLI), continuous subcutaneous apomorphine infusions (CSAI) and Magnetic Resonance guided Focused Ultrasound (MRgFUS) in recent years. To achieve good outcomes with any of these therapeutic modalities, careful patient selection, multidisciplinary evaluation and technical expertise are equally important. In this review, we will provide an overview of the neuromodulation strategies currently available for PD, emphasizing on patient selection and choosing among the various strategies.

Peripheral Neuromodulation for Chronic Pain.

BACKGROUND: Chronic, focal, neuropathic pain is difficult to treat. Local nerve blocks are either ineffective or do not last. Regular neuromodulation modalities like spinal cord stimulation (SCS) or pain pump are invasive and affect a larger area. OBJECTIVES: To discuss the indications, technique, nuances, programming, and outcomes of peripheral neuromodulation. METHODS: The article reviews published literature and the author's own experience of over 500 cases of peripheral neuromodulation. RESULTS AND CONCLUSION: Peripheral neuromodulation using peripheral nerve field stimulation (PNFS) is an effective, minimally invasive, targeted method of treatment. It is a relatively new modality in the field of neuromodulation but is used more often.

Deep Brain Stimulation and Motor Cortex Stimulation for Chronic Pain.

Deep brain stimulation (DBS) and Motor Cortex stimulation (MCS) have been used for control of chronic pain. Chronic pain of any origin is complex and difficult to treat. Stimulation of various areas in brain-like sensory thalamus, medial nuclei of thalamus including centro-lateral nucleus of thalamus (CL), periaqueductal gray, periventricular gray, nucleus accumbence and motor cortex provides partial relief in properly selected patients. This article reviews the pain pathways, theories of pain, targets for DBS and rationale of DBS and MCS. It also discusses the patient selection, technical details of each target.

Deep Brain Stimulation for Refractory Depression, Obsessive-Compulsive Disorder and Addiction.

BACKGROUND: Depression, Obsessive-compulsive Disorder (OCD), and addiction are the leading disabling psychiatric conditions with huge health care and psychosocial burden besides increased morbidity and mortality. Deep brain stimulation (DBS) for depression, OCD, and addiction is increasingly explored and is quite challenging. We present a brief review of the pertinent literature of DBS for depression, OCD, and addiction and present the status and challenges. OBJECTIVE: The aim of this study was to review the current status and challenges with the DBS for Depression, Obsessive-compulsive Disorder (OCD), and addiction. METHOD: The pertinent brief literature was reviewed in reference to the DBS for Depression, Obsessive-compulsive Disorder (OCD), and addiction. RESULTS: To date, OCD is the only psychiatric condition approved for DBS therapy (under humanitarian device exemption). Although the initial encouraging results of DBS in depression were encouraging but the two larger multicenter clinical trials failed to meet the primary objective. Further evaluation and studies are ongoing. Similarly, the initial results of DBS for addiction are encouraging; however, the experience is limited. CONCLUSION: DBS for depression, OCD, and addiction seem challenging but promising. Further refinement of the target and evaluation in a larger and controlled setting is needed, specifically for depression and addiction.

Neuromodulation in Obstructive Sleep Apnea.

Epidemiological studies show a steady rise in the prevalence of obstructive sleep apnea (OSA). Untreated OSA is responsible for numerous chronic health conditions, motor vehicle, and workplace-related accidents leading to substantial economic burden both to the individual and society. Multiple causes for OSA and a wide range of consequences has made its diagnosis and treatment difficult. Obstructive sleep apnea may be caused by anatomical variation, increased collapsibility of the upper airway, low sleep arousal threshold, and exaggerated response to desaturation. Lifestyle changes, anatomical corrective surgeries, and oral appliances have been used but patient compliance is poor as it interferes in the daily routine. Neuromodulation is a promising functional modifying option that addresses the cause of obstructive sleep apnea at multiple levels.

Direct Comparison of Posterior Subthalamic Area Stimulation versus Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

In this case report, we describe successful tremor capture via stimulation of the posterior subthalamic area (PSA) for a patient with tremor-predominant Parkinson's disease. In this scenario, the patient had a deep brain stimulation (DBS) lead placed in the PSA of the right hemisphere and a DBS lead placed in the subthalmic nucleus (STN) of the left hemisphere. Therefore, we were able to directly compare tremor capture in the same patient receiving stimulation in two different brain areas. We show that both placements are equally efficacious for tremor suppression, though the DBS lead placed in the PSA required slightly higher current intensity. This comparison in the same patient confirms that stimulation of the PSA can successfully suppress tremor in Parkinson's disease.

Predicting extended hospital stay after deep brain stimulation surgery in Parkinson's patients.

BACKGROUND: The goal of deep brain stimulation (DBS) is to achieve maximal benefit for the patient while minimizing the likelihood of adverse effects. Currently, no standardized criteria exist that predicts extended hospital stay in DBS patients, although careful patient selection is recognized as a very important step for successful DBS therapy. OBJECTIVES AND METHODS: The objective of this study was to identify eight key factors that predicted extended post-operative hospital stay following DBS lead implantation, in an effort to better identify patients that would require minimal hospital stay, resulting in reduced cost and reduced exposure to hospital- related problems. Univariate logistic regression models were used to examine associations between each factor and patients' post-surgical outcomes. RESULTS: Using data collected from 183 patients, we found that 53 patients required a hospital stay longer than two days within one month post-procedure. Those who were 70 years or older and those who had frequent falls were significantly more likely to require extended post-surgical care. Patients that scored three points or higher on our eight-factor assessment scale had a greater likelihood of experiencing an event that would require an extended hospital stay following DBS lead placement, regardless of what three factors were present. CONCLUSIONS: Any PD patient who is 70 years or older, incurring frequent falls, or with more than three points on our scale, should be carefully screened and cautioned about likely prolonged recovery and extended post-operative hospital stay.

Connectivity-based selection of optimal deep brain stimulation contacts: A feasibility study.

BACKGROUND: The selection of optimal deep brain stimulation (DBS) parameters is time-consuming, experience-dependent, and best suited when acute effects of stimulation can be observed (e.g., tremor reduction). OBJECTIVES: To test the hypothesis that optimal stimulation location can be estimated based on the cortical connections of DBS contacts. METHODS: We analyzed a cohort of 38 patients with Parkinson's disease (24 training, and 14 test cohort). Using whole-brain probabilistic tractography, we first mapped the cortical regions associated with stimulation-induced efficacy (rigidity, bradykinesia, and tremor improvement) and side effects (paresthesia, motor contractions, and visual disturbances). We then trained a support vector machine classifier to categorize DBS contacts into efficacious, defined by a therapeutic window ≥2 V (threshold for side effect minus threshold for efficacy), based on their connections with cortical regions associated with efficacy versus side effects. The connectivity-based classifications were then compared with actual stimulation contacts using receiver-operating characteristics (ROC) curves. RESULTS: Unique cortical clusters were associated with stimulation-induced efficacy and side effects. In the training dataset, 42 of the 47 stimulation contacts were accurately classified as efficacious, with a therapeutic window of ≥3 V in 31 (66%) and between 2 and 2.9 V in 11 (24%) electrodes. This connectivity-based estimation was successfully replicated in the test cohort with similar accuracy (area under ROC = 0.83). CONCLUSIONS: Cortical connections can predict the efficacy of DBS contacts and potentially facilitate DBS programming. The clinical utility of this paradigm in optimizing DBS outcomes should be prospectively tested, especially for directional electrodes.

The relative effects of dexmedetomidine and propofol on cerebral blood flow velocity and regional brain oxygenation: A randomised noninferiority trial.

BACKGROUND: Dexmedetomidine constricts cerebral blood vessels without a concomitant reduction in cerebral metabolic oxygen consumption. Its safety as a sedative in patients with neurological diseases thus remains uncertain. OBJECTIVE: Our primary objective was to test the hypothesis that dexmedetomidine is noninferior to propofol as regards cerebral blood flow (CBF) velocity and brain oxygenation. DESIGN: Unblinded randomised trial. SETTING: Cleveland Clinic Hospital, Cleveland, from November 2010 to July 2013. PATIENTS: Forty-four patients scheduled for insertion of a deep-brain stimulating electrodes. INTERVENTIONS: Patients were randomised to receive either dexmedetomidine or propofol sedation during deep-brain stimulating electrode insertion. MAIN OUTCOME MEASURES: Intraoperative CBF velocity was measured with transcranial Doppler, and brain oxygenation was assessed with near-infrared spectroscopy. Noninferiority of dexmedetomidine to propofol was defined as a less than 20% difference in means. RESULTS: Twenty-three patients were given dexmedetomidine and 21 propofol. Baseline characteristics and operative management were similar in each group. Dexmedetomidine was noninferior to propofol on both CBF and brain oxygenation, confirming our primary hypothesis. For cerebral flood flow, the estimated ratio of means (dexmedetomidine/propofol) was 0.94 [90% CI: 0.84 to 1.05], P = 0.011 for noninferiority. For brain oxygenation, the estimated ratio of means was 0.99 [90% CI: 0.96 to 1.02], P < 0.001 for noninferiority. Superiority was not found for either primary outcome. Dexmedetomidine provided deeper sedation than propofol, with a difference of medians of 1 [90% CI: 0 to 2], P < 0.001 on the Observer's Assessment of Alertness/Sedation scale. No significant differences were observed in pulsatility index, cerebral perfusion pressure, number of hypertensive or apnoeic episodes. CONCLUSION: Regional brain oxygenation and CBF velocity are comparably preserved during dexmedetomidine and propofol sedation. Thus, the use of dexmedetomidine in patients with movement disorders appears reasonable. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT 01200433).

Intraoperative Hypotension During Second Stage of Deep Brain Stimulator Placement: Same Day versus Different Day Procedures.

BACKGROUND: We evaluated blood pressure management associated with implantable pulse generator (IPG) procedure on same day (SD) versus different day (DD) from deep brain stimulation (DBS) placement. METHODS: A retrospective chart review of 99 records for vasopressors given during IPG using a negative binomial regression model was performed. An association between SD versus DD, cumulative vasopressor dose, and minimum and maximum mean arterial pressure (MAP) were sought. RESULTS: No significant association between SD versus DD DBS and the number of times vasopressors were given during stage II, estimated ratio of means (CI) of 1.8 (0.9-3.5); P = 0.07. Day of stage II had no association with the cumulative dose of vasopressor given during stage II, with an estimated difference in means (CI) of 2.4 (-0.4 to 5.3). The SD group had a significantly lower mean of minimum stage II MAP compared with DD, with an estimated difference in means (CI) of -10.5 (-17.4 to -3.5; P < 0.001). There was no association with maximum stage II MAP, with an estimated difference in means (CI) of -2.8 (-17.6 to 12.0; P = 0.63). CONCLUSION: No difference in intraoperative vasopressor use was found between SD versus DD IPG placement, but the SD group had a significantly lower minimum MAP.

Sandwich technique, peripheral nerve stimulation, peripheral field stimulation and hybrid stimulation for inguinal region and genital pain.

OBJECTIVE: Ilioinguinal neuralgia (IG) and genitofemoral (GF) neuralgia following inguinal hernia repair is a chronic and debilitating neuropathic condition. Recently, peripheral nerve stimulation has become an effective and minimally invasive option for the treatment of refractory pain. Here we present a retrospective case series of six patients who underwent placement of peripheral nerve stimulation electrodes using various techniques for treatment of refractory post-intervention inguinal region pain. METHODS: Six patients with post-intervention inguinal, femoral or GF neuropathic pain were evaluated for surgery. Either octopolar percutaneous electrodes or combination of paddle and percutaneous electrodes were implanted in the area of their pain. Pain visual analog scores (VAS), surgical complication rate, preoperative symptom duration, degree of pain relief, preoperative and postoperative work status, postoperative changes in medication usage, and overall degree of satisfaction with this therapy was assessed. RESULTS: All six patients had an average improvement of 62% in the immediate post-operative follow-up. Four patients underwent stimulation for IG, one for femoral neuralgia, and another for GF neuralgia. Peripheral nerve stimulation provided at least 50% pain relief in all the six patients with post-intervention inguinal region pain. 85% of patients indicated they were completely satisfied with the therapy overall. There was one treatment failure with an acceptable complication rate. CONCLUSION: Peripheral nerve or field stimulation for post-intervention inguinal region pain is a safe and effective treatment for this refractory and complex problem for patients who have exhausted other management options.