Long-term safety of spinal cord stimulation systems in a prospective, global registry of patients with chronic pain.

Aim: The availability of long-term (>2 years) safety outcomes of spinal cord stimulation (SCS) remains limited. We evaluated safety in a global SCS registry for chronic pain. Methods: Participants were prospectively enrolled globally at 79 implanting centers and followed out to 3 years after device implantation. Results: Of 1881 participants enrolled, 1289 received a permanent SCS implant (1776 completed trial). The annualized rate of device explant was 3.5% (all causes), and 1.1% due to inadequate pain relief. Total incidence of device explantation >3 years was 7.6% (n = 98). Of these, 32 subjects (2.5%) indicated inadequate pain relief as cause for removal. Implant site infection (11 events) was the most common device-related serious adverse event (<1%). Conclusion: This prospective, global, real-world study demonstrates a high-level of safety for SCS with low rate of explant/serious adverse events. Clinical Trial Registration: NCT01719055 (ClinicalTrials.gov).

Classification of Qualitative Fieldnotes Collected During Quantitative Sensory Testing: A Step Towards the Development of a New Mixed Methods Approach in Pain Research.

PURPOSE: Quantitative sensory testing (QST) is a standardized method to assess somatosensory function. The collection of qualitative information, during the QST procedure, could be an interesting way to facilitate the characterization of altered sensory perception and the identification of different pain phenotypes. The aims of this study were 1) to classify qualitative fieldnotes of sensory abnormalities collected during an independent QST study, and 2) to generate a qualitative interview guide that could be included in the traditional QST procedure as a step towards the implementation of a mixed methods approach. PATIENTS AND METHODS: QST data were collected from 48 chronic neuropathic pain patients treated with spinal cord stimulation (SCS). Three body areas, with or without SCS, were tested: the painful limb targeted by SCS, the contralateral area, and the ipsilateral upper limb. After each trial of each QST modality, patients were encouraged to report any sensory abnormalities they could identify with a pain quality scale or using their own words. RESULTS: Qualitative self-reported sensory abnormalities were dichotomized into two groups: altered sensory intensities and altered sensory perceptions. Altered sensory intensities were classified as sensory loss or sensory gain subgroups. Altered sensory perceptions were classified as paresthesia and dysesthesia subgroups Overall, 630 qualitative fieldnotes of altered sensations were collected: 385 on the painful limb, 173 at the contralateral area, and 72 at the ipsilateral upper limb. Based on these qualitative data, we propose a standardized method to collect qualitative data involving 9 open- and close-ended questions and 21 codes. CONCLUSION: Our findings have highlighted the value of qualitative sensory evaluation during QST and constitute an important milestone in the development of a mixed methods protocol in phenotyping research.

Rise of Raman spectroscopy in neurosurgery: a review.

SIGNIFICANCE: Although the clinical potential for Raman spectroscopy (RS) has been anticipated for decades, it has only recently been used in neurosurgery. Still, few devices have succeeded in making their way into the operating room. With recent technological advancements, however, vibrational sensing is poised to be a revolutionary tool for neurosurgeons. AIM: We give a summary of neurosurgical workflows and key translational milestones of RS in clinical use and provide the optics and data science background required to implement such devices. APPROACH: We performed an extensive review of the literature, with a specific emphasis on research that aims to build Raman systems suited for a neurosurgical setting. RESULTS: The main translatable interest in Raman sensing rests in its capacity to yield label-free molecular information from tissue intraoperatively. Systems that have proven usable in the clinical setting are ergonomic, have a short integration time, and can acquire high-quality signal even in suboptimal conditions. Moreover, because of the complex microenvironment of brain tissue, data analysis is now recognized as a critical step in achieving high performance Raman-based sensing. CONCLUSIONS: The next generation of Raman-based devices are making their way into operating rooms and their clinical translation requires close collaboration between physicians, engineers, and data scientists.

Effects of Tonic Spinal Cord Stimulation on External Mechanical and Thermal Stimuli Perception Using Quantitative Sensory Testing: A Multicenter Stimulation ON-OFF Study on Chronic Pain Patients.

OBJECTIVES: Tonic spinal cord stimulation (SCS) is currently used to treat neuropathic pain. With this type of stimulation, an implantable pulse generator generates electrical paresthesias in the affected area through 1 or more epidural leads. The goal of this study was to evaluate the impact of tonic SCS on the sensory perception of chronic pain patients using quantitative sensory testing (QST). MATERIALS AND METHODS: Forty-eight patients (mean age: 57 y) with chronic leg pain due to failed back surgery syndrome or complex regional pain syndrome treated with SCS were recruited from 3 research centers. Test procedures included 2 sessions (stimulation On or Off), with measures of detection thresholds for heat, touch, vibration, and of pain thresholds for cold, heat, pressure, the assessment of dynamic mechanical allodynia, and temporal pain summation. Three different areas were examined: the most painful area of the most painful limb covered with SCS-induced paresthesias (target area), the contralateral limb, and the ipsilateral upper limb. Wilcoxon signed-rank tests were used to compare the mean difference between On and Off for each QST parameter at each area tested. P-values <0.05 were considered significant. RESULTS: Regarding the mean difference between On and Off, patients felt less touch sensation at the ipsilateral area (-0.4±0.9 g, P=0.0125) and were less sensitive at the contralateral area for temporal pain summation (-4.9±18.1 on Visual Analog Scale 0 to 100, P=0.0056) with SCS. DISCUSSION: It is not clear that the slight changes observed were clinically significant and induced any changes in patients' daily life. Globally, our results suggest that SCS does not have a significant effect on sensory perception.

Occipital nerve stimulation for non-migrainous chronic headaches: a systematic review protocol.

BACKGROUND: Defined as a headache lasting at least 15 days per month, chronic headache is reported by 3% of the general population, and a substantial proportion of them are refractory to current therapies. Occipital nerve stimulation (ONS) is a treatment option, but is still considered as a last resort treatment especially because of its invasive nature and the cost associated. Some reviews reported a limited efficacy of ONS for the treatment of migraines, with a high risk of complications. However, results reporting its efficacy and safety on other headache disorders are unclear. The aim of this review is to assess the efficacy and safety of ONS in regards to non-migrainous chronic headaches. METHODS: We will conduct a systematic review and meta-analysis of studies evaluating the use of ONS in comparison to sham stimulation or the best available treatment in patients with chronic headache. MEDLINE, CINHAL, EMBASE, PsycINFO, ECRI Institute Library, WIKISTIM, the Cochrane Library databases, and clinical trial registries will be searched for eligible studies. The review will include adult patients diagnosed with chronic headache excluding migraine. Two independent reviewers will process to the screening of studies according to titles, abstracts, and then full texts. The primary outcome is the overall reduction of head pain severity. The secondary outcomes are rates of reduction in the severity of head pain, headache frequency, and duration, use of medication, impairment, quality of life, healthcare utilization, return to work, and adverse events. Extracted data will include patients' and procedure characteristics, details on comparative treatment or sham, and clinical outcomes. The risk of bias of the studies will be also independently assessed using the Cochrane risk of bias tools. DISCUSSION: This systematic review will allow us to better evaluate the potential role of ONS for the treatment of patients with chronic headache that are refractory to less invasive therapies. It will help to determine the degree of safety of ONS. Moreover, it will help to design and conduct future randomized controlled trials focused on patients who may better respond to such treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121623.

Intraoperative fiber optic guidance during chronic electrode implantation in deep brain stimulation neurosurgery: proof of concept in primates.

OBJECTIVE: The clinical outcome of deep brain stimulation (DBS) surgery relies heavily on the implantation accuracy of a chronic stimulating electrode into a small target brain region. Most techniques that have been proposed to precisely target these deep brain regions were designed to map intracerebral electrode trajectory prior to chronic electrode placement, sometimes leading to positioning error of the final electrode. This study was designed to create a new intraoperative guidance tool for DBS neurosurgery that can improve target detection during the final implantation of the chronic electrode. METHODS: Taking advantage of diffuse reflectance spectroscopy, the authors developed a new surgical tool that senses proximal brain tissue through the tip of the chronic electrode by means of a novel stylet, which provides rigidity to DBS leads and houses fiber optics. RESULTS: As a proof of concept, the authors demonstrated the ability of their noninvasive optical guidance technique to precisely locate the border of the subthalamic nucleus during the implantation of commercially available DBS electrodes in anesthetized parkinsonian monkeys. Innovative optical recordings combined to standard microelectrode mapping and detailed postmortem brain examination allowed the authors to confirm the precision of optical target detection. They also show the optical technique's ability to detect, in real time, upcoming blood vessels, reducing the risk of hemorrhage during the chronic lead implantation. CONCLUSIONS: The authors present a new optical guidance technique that can detect target brain regions during DBS surgery from within the implanted electrode using a proof of concept in nonhuman primates. The technique discriminates tissue in real time, contributes no additional invasiveness to the procedure by being housed within the electrode, and can provide complementary information to microelectrode mapping during the implantation of the chronic electrode. The technique may also be a powerful tool for providing direct anatomical information in the case of direct implantations wherein microelectrode mapping is not performed.

Effects of Tonic Spinal Cord Stimulation on Sensory Perception in Chronic Pain Patients: A Systematic Review.

OBJECTIVES: Even if spinal cord stimulation (SCS) is widely used and effective in treating intractable chronic neuropathic pain conditions, little is known about its possible impacts on sensory perception. Quantitative sensory testing (QST) is a useful tool to assess this issue. The aim of this study was to review the impact of tonic SCS on somatosensory perception quantified by QST in chronic pain patients. MATERIALS AND METHODS: Relevant articles and abstracts were searched in all languages from CINAHL, Cochrane, Embase, MEDLINE, and Web of Knowledge data bases. Data were extracted and included studies were assessed for risk of bias. RESULTS: Out of 5610 records, 15 peer-reviewed articles were eligible and included. The results are heterogeneous due to inadequate comparability among studies for populations (a total of 224 patients diagnosed with more than 13 chronic pain conditions), QST parameters (22 measured with 25 different devices) and experimental procedures (study design, comparator, evaluation time, and area tested). The wide variety of studies, designs, populations, and measures included in this review did not lead to strong evidence on how conventional ("tonic") SCS affects sensory processing in patients with chronic pain. CONCLUSIONS: The data available tend to suggest that conventional SCS does not interfere with perception of external stimuli. New studies that follow a standardized procedure and consider the possible influence of sensory profile, after-effect bias, and confounding factors are required to confirm this observation. Moreover, the impact on sensory perception of other SCS modalities and alternative electrical neuromodulation therapies could also be explored.

Canadian Assessment of Deep Brain Stimulation Access: The Canada Study.

BACKGROUND: The Canada Health Act requires reasonable access to all medically necessary therapies. No information is available to assess the current access to neuromodulation across Canada. This study quantifies the current rate of deep brain stimulation (DBS) for the entire country of Canada. Analyses were performed to determine whether there were differences in access based on provincial or territorial location, rural or non-rural region, or socioeconomic status. METHODS: All implanted DBS devices in Canada over a 2-year epoch (January 2015 to December 2016) were supplied by either Boston Scientific or Medtronic. Investigators received anonymized data from these companies, including patient age and home residence region. The 2016 Statistics Canada census data were used to determine the rate of DBS surgery and whether access was related to provincial location, rural versus non-rural region or socioeconomic status. RESULTS: A total of 722 patients were studied. The rate of DBS surgery for the entire country was ten per million population per year. Saskatchewan was significantly above (374%) the national average, whereas Quebec (40%) and Newfoundland & Labrador (32%) were significantly below the national average. No patients from the three territories received DBS. There were no significant differences in access from rural versus non-rural areas or in regions within provinces with different socioeconomic status. CONCLUSIONS: This is the first study to quantify all patients receiving DBS within an entire country. The current rate of DBS surgery within Canada is ten cases per million per year. Statistically significant regional differences were discovered and discussed.

A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. METHODS: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented. RESULTS: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. CONCLUSIONS: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications.

Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson's Disease.

Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD.

Corrigendum to "Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson's Disease".

[This corrects the article DOI: 10.1155/2014/487035.].

The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson's disease.

The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) on different language abilities are still controversial and its impact on high-level language abilities such as metaphor comprehension has been overlooked. The aim of this study was to determine the effects of STN electrical stimulation on metaphor comprehension and language abilities such as lexical and semantic capacities. Eight PD individuals with bilateral STN-DBS were first evaluated OFF-DBS and, at least seven weeks later, ON-DBS. Performance on metaphor comprehension, lexical decision, word association and verbal fluency tasks were compared ON and OFF-DBS in addition to motor symptoms evaluation. STN stimulation had a significant beneficial effect on motor symptoms in PD. However, this stimulation did not have any effect on metaphor comprehension or any other cognitive ability evaluated in this study. These outcomes suggest that STN stimulation may have dissociable effects on motor and language functions.

Changes in vowel articulation with subthalamic nucleus deep brain stimulation in dysarthric speakers with Parkinson's disease.

Purpose. To investigate changes in vowel articulation with the electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) in dysarthric speakers with Parkinson's disease (PD). Methods. Eight Quebec-French speakers diagnosed with idiopathic PD who had undergone STN DBS were evaluated ON-stimulation and OFF-stimulation (1 hour after DBS was turned off). Vowel articulation was compared ON-simulation versus OFF-stimulation using acoustic vowel space and formant centralization ratio, calculated with the first (F1) and second formant (F2) of the vowels /i/, /u/, and /a/. The impact of the preceding consonant context on articulation, which represents a measure of coarticulation, was also analyzed as a function of the stimulation state. Results. Maximum vowel articulation increased during ON-stimulation. Analyses also indicate that vowel articulation was modulated by the consonant context but this relationship did not change with STN DBS. Conclusions. Results suggest that STN DBS may improve articulation in dysarthric speakers with PD, in terms of range of movement. Optimization of the electrical parameters for each patient is important and may lead to improvement in speech fine motor control. However, the impact on overall speech intelligibility may still be small. Clinical considerations are discussed and new research avenues are suggested.

Intrathecal morphine therapy-related granulomas: faster to grow than thought.

Complications of intrathecal drug delivery are relatively rare. Of these, infections, cutaneous erosion, and granulomas account for the most common complications. The latter is often noticed when the patient shows signs of sedation and/or reduced pain relief. Granulomas have always been considered to develop over a long period of time, usually calculated in months. Here, we present a case where a catheter-tip granuloma formed within 5 weeks of intrathecal morphine. The patient was carrying an intrathecal pump for 3 months when it was diagnosed. Probable causes of the formation are discussed.

Global nitrogen fertilizer supply and demand outlook.

This paper presents a brief overview of the world nitrogen fertilizer demand, highlights trends in the global and regional developments of production capacity and provides a medium-term perspective of the global nitrogen supply/demand balance.