Human brain tissue identification using coherent anti-Stokes Raman scattering spectroscopy and diffuse reflectance spectroscopy for deep brain stimulation surgery.

Significance: We assess the feasibility of using diffuse reflectance spectroscopy (DRS) and coherent anti-Stokes Raman scattering spectroscopy (CARS) as optical tools for human brain tissue identification during deep brain stimulation (DBS) lead insertion, thereby providing a promising avenue for additional real-time neurosurgical guidance. Aim: We developed a system that can acquire CARS and DRS spectra during the DBS surgery procedure to identify the tissue composition along the lead trajectory. Approach: DRS and CARS spectra were acquired using a custom-built optical probe integrated in a commercial DBS lead. The lead was inserted to target three specific regions in each of the brain hemispheres of a human cadaver. Spectra were acquired during the lead insertion at constant position increments. Spectra were analyzed to classify each spectrum as being from white matter (WM) or gray matter (GM). The results were compared with tissue classification performed on histological brain sections. Results: DRS and CARS spectra obtained using the optical probe can identify WM and GM during DBS lead insertion. The tissue composition along the trajectory toward a specific target is unique and can be differentiated by the optical probe. Moreover, the results obtained with principal component analysis suggest that DRS might be able to detect the presence of blood due to the strong optical absorption of hemoglobin. Conclusions: It is possible to use optical measurements from the DBS lead during surgery to identify WM and GM and possibly the presence of blood in human brain tissue. The proposed optical tool could inform the surgeon during the lead placement if the lead has reached the target as planned. Our tool could eventually replace microelectrode recordings, which would streamline the process and reduce surgery time. Further developments are required to fully integrate these tools into standard clinical procedures.

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.

Levodopa partially rescues microglial numerical, morphological, and phagolysosomal alterations in a monkey model of Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative motor disorder. The mechanisms underlying the onset and progression of Levodopa (L-Dopa)-induced dyskinesia (LID) during PD treatment remain elusive. Emerging evidence implicates functional modification of microglia in the development of LID. Thus, understanding the link between microglia and the development of LID may provide the knowledge required to preserve or promote beneficial microglial functions, even during a prolonged L-Dopa treatment. To provide novel insights into microglial functional alterations in PD pathophysiology, we characterized their density, morphology, ultrastructure, and degradation activity in the sensorimotor functional territory of the putamen, using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cynomolgus monkeys. A subset of MPTP monkeys was treated orally with L-Dopa and developed LID similar to PD patients. Using a combination of light, confocal and transmission electron microscopy, our quantitative analyses revealed alterations of microglial density, morphology and phagolysosomal activity following MPTP intoxication that were partially normalized with L-Dopa treatment. In particular, microglial density, cell body and arborization areas were increased in the MPTP monkeys, whereas L-Dopa-treated MPTP animals presented a microglial phenotype similar to the control animals. At the ultrastructural level, microglia did not differ between groups in their markers of cellular stress or aging. Nevertheless, microglia from the MPTP monkeys displayed reduced numbers of endosomes, compared with control animals, that remained lower after L-Dopa treatment. Microglia from MPTP monkeys treated with L-Dopa also had increased numbers of primary lysosomes compared with non-treated MPTP animals, while secondary and tertiary lysosomes remained unchanged. Moreover, a decrease microglial immunoreactivity for CD68, considered a marker of phagocytosis and lysosomal activity, was measured in the MPTP monkeys treated with L-Dopa, compared with non-treated MPTP animals. Taken together, these findings revealed significant changes in microglia during PD pathophysiology that were partially rescued by L-Dopa treatment. Albeit, this L-Dopa treatment conferred phagolysosomal insufficiency on microglia in the dyskinetic Parkinsonian monkeys.

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.

Microglial Implication in Parkinson's Disease: Loss of Beneficial Physiological Roles or Gain of Inflammatory Functions?

Microglia, often described as the brain-resident macrophages, play crucial roles in central nervous system development, maintenance, plasticity, and adaptation to the environment. Both aging and chronic stress promote microglial morphological and functional changes, which can lead to the development of brain pathologies including Parkinson's disease (PD). Indeed, aging, and chronic stress represent main environmental risk factors for PD. In these conditions, microglia are known to undergo different morphological and functional changes. Inflammation is an important component of PD and disequilibrium between pro- and anti-inflammatory microglial functions might constitute a crucial component of PD onset and progression. Cumulated data also suggest that, during PD, microglia might lose beneficial functions and gain detrimental ones, in addition to mediating inflammation. In this mini-review, we aim to summarize the literature discussing the functional and morphological changes that microglia undergo in PD pathophysiology and upon exposure to its two main environmental risk factors, aging, and chronic stress.

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.

Bilateral stereotactic anterior capsulotomy for obsessive-compulsive disorder: long-term follow-up.

BACKGROUND AND PURPOSE: Psychosurgery, such as anterior capsulotomy, is a therapeutic option for treatment-resistant obsessive-compulsive disorder (OCD). In this paper, we present a prospective, long-term follow-up study aimed at evaluating both the efficacy and the safety of anterior capsulotomy for the treatment of severe, refractory OCD. METHODS: Twenty-four patients were surgically treated in our centre between 1997 and 2009, 19 of whom were included in this study. Patients were assessed at 3, 6, 12, and 24 months and last follow-up (mean of 7 years) was carried out by phone. OCD symptom severity was evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A patient with an improvement rate of over 35% in the Y-BOCS score was considered a responder, while a patient with a 25% improvement was considered a partial responder. RESULTS: With a mean improvement of 31% in the Y-BOCS score at long-term follow-up, 36.8% of the patients responded fully to the procedure and 10.5% were considered partial responders, for an overall response rate of 47.3% of patients. At the end of the study, 3/19 patients had recovered (Y-BOCS score <8) and 3/19 were in remission (Y-BOCS score <16). No cases of mortality were reported and the overall adverse event rate was 57.9%. Only 2 patients had permanent surgical complications. CONCLUSIONS: Anterior capsulotomy is an effective and safe technique for the treatment of severe refractory OCD in patients who have no other alternative to improve their symptoms.

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.