Repeat Surgery for Recurrent or Refractory Trigeminal Neuralgia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Surgery can effectively treat Trigeminal neuralgia (TN), but postoperative pain recurrence or nonresponse are common. Repeat surgery is frequently offered but limited data exist to guide the selection of salvage surgical procedures. We aimed to compare pain relief outcomes after repeat microvascular decompression (MVD), percutaneous rhizotomy (PR), or stereotactic radiosurgery (SRS) to determine which modality was most efficacious for surgically refractory TN. METHODS: A PRISMA systematic review and meta-analysis was performed, including studies of adults with classical or idiopathic TN undergoing repeat surgery. Primary outcomes included complete (CPR) and adequate (APR) pain relief at last follow-up, analyzed in a multivariate mixed-effect meta-regression of proportions. Secondary outcomes were initial pain relief and facial numbness. RESULTS: Of 1299 records screened, 61 studies with 68 treatment arms (29 MVD, 14 PR, and 25 SRS) comprising 2165 patients were included. Combining MVD, PR, and SRS study data, 68.8% achieved initial CPR after a repeat TN procedure. On average, 49.6% of the combined sample of MVD, PR, and SRS had CPR at final follow-up, which was on average 2.99 years postoperatively. The proportion (with 95% CI) achieving CPR at final follow-up was 0.57 (0.51-0.62) for MVD, 0.60 (0.52-0.68) for PR, and 0.35 (0.30-0.41) for SRS, with a significantly lower proportion of pain relief with SRS. Estimates of initial CPR for MVD were 0.82 (0.78-0.85), 0.68 for PR (0.6-0.76), and 0.41 for SRS (0.35-0.48). CONCLUSIONS: Across MVD, PR, and SRS, about half of TN patients maintain complete CPR at an average follow-up time of 3 years after repeat surgery. In treating refractory or recurrent TN, MVD and PR were superior to SRS in both initial pain relief and long-term pain relief at final follow-up. These findings can inform surgical decision-making in this challenging population.

Heightened presence of inflammatory mediators in the cerebrospinal fluid of patients with trigeminal neuralgia.

Introduction: Trigeminal neuralgia (TN) is a chronic, debilitating facial pain disease causing stabbing pain attacks in the sensory distribution of the trigeminal nerve. The underlying pathophysiology of TN is incompletely understood, although microstructural abnormalities consistent with focal demyelination of the trigeminal nerve root have been shown in patients with TN. Studies of the cerebrospinal fluid (CSF) in patients with TN suggest an increased prevalence of inflammatory mediators, potentially implicating neuroinflammation in the pathophysiology of TN, as it has been implicated in other chronic pain conditions. Objectives: This study aimed to further assess the inflammatory profile of CSF in TN. Methods: Cerebrospinal fluid was collected from 8 medically refractory patients with TN undergoing microvascular decompression surgery and 4 pain-free controls (2 with hemifacial spasm; 2 with normal pressure hydrocephalus). Cerebrospinal fluid was collected from the cerebellopontine angle cistern intraoperatively in the patients with TN. Inflammatory profiles of CSF samples were analyzed using a 71-plex cytokine and chemokine multiplex assay. Results: Ten inflammatory markers were found to be significantly higher in TN CSF, and no analytes were significantly lower. Elevated factors can be classified into pro-inflammatory cytokines (IL-9, IL-18, and IL-33), chemokines (RANTES and ENA-78), the tumor necrosis factor superfamily (TRAIL and sCD40L), and growth factors (EGF, PDGF-AB/BB, and FGF-2). Conclusion: This study further supports the notion that neuroinflammation is present in TN, and that multiple molecular pathways are implicated.

Emerging Neurotechnologies: Implications for Professional Relations and Communication.

Rapid advances in neurotechnology and neurosurgery are positioned to revolutionize care for patients suffering from debilitating neurological and psychiatric disease. Enthusiasm for the adoption of these technologies is tempered by ethical dilemmas regarding resource allocation, provision of care, communication with patients and other providers, and other potential pitfalls. In the present work, we discuss bioethical implications of novel neurotechnologies for medical practice. In particular, we examine the implications of neurotechnological advancement through the lens of professional communication. Emerging challenges within this domain are presented in the context of physician interactions with four key partners: (i) patients; (ii) other physicians; (iii) industry; and (iv) society-at-large. Anticipated issues as well as mitigation strategies are discussed as they relate to communication with these stakeholders.

Comparison of Prognostic Scoring Systems to Predict Durable Pain Relief After Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND: Microvascular decompression (MVD) is an effective treatment for trigeminal neuralgia, but pain recurs in a substantial minority of patients. Two recently published scoring systems by Hardaway et al. and Panczykowski et al. use simple preoperative clinical and imaging features to predict durable pain relief following MVD, but their predictive performance has not been independently validated. This study aimed to compare predictive performance of the Hardaway et al. score (HS) and Panczykowski et al. score (PS) for 1-year, 3-year, and long-term pain-free outcomes after MVD for trigeminal neuralgia. METHODS: HS and PS were computed for a retrospective, single-institution cohort of 68 patients with trigeminal neuralgia who underwent MVD. Primary outcome was pain recurrence after MVD. Predictive performance of HSs and PSs was evaluated with area under the curve sensitivity analysis and regression models for survival analyses at 1 year, 3 years, and last follow-up. RESULTS: Area under the curve for predicting pain-free outcome was higher for PS versus HS at 1 year (0.873 vs. 0.775) and 3 years (0.793 vs. 0.704). Cox proportional hazard models showed that PS better predicted long-term pain-free outcomes compared with HS (P < 0.05). One-year pain-free outcome was best predicted by pain type; longer-term outcomes were better predicted by presence and degree of neurovascular compression on preoperative imaging. CONCLUSIONS: PS is superior to HS in predicting pain-free outcomes after MVD, which may aid in patient selection and counseling. Overall, more significant neurovascular compression of the trigeminal nerve root, and to a lesser extent classical paroxysmal pain, are good predictors of durable pain relief after MVD.

Effect of Motor State on Postactivation Depression of the Soleus H-Reflex in Parkinson's Disease During Deep Brain Stimulation and Dopaminergic Medication Treatment: A Pilot Study.

PURPOSE: Postactivation depression of the Hoffmann reflex is reduced in Parkinson's disease (PD), but how the recovery is influenced by the state of the muscle is unknown. The present pilot study examined postactivation depression in PD at rest and during a voluntary contraction while patients were off treatment and while receiving medications and/or deep brain stimulation. METHODS: The authors recruited nine patients with PD treated with implanted deep brain stimulation and examined postactivation depression under four treatment conditions. Paired pulses were delivered 25 to 300 ms apart, and soleus Hoffmann reflex recovery was tested at rest and during voluntary plantar flexion. Trials were matched for background muscle activity and compared with 10 age-matched controls. RESULTS: Patients with Parkinson disease who were OFF medications (OFF meds) and OFF stimulation (OFF stim) at rest showed less postactivation depression at the 300 ms interpulse interval (86.1% ± 21.0%) relative to control subjects (36.4% ± 6.1%; P < 0.05). Postactivation depression was restored when dopaminergic medication and/or deep brain stimulation was applied. Comparisons between resting and active motor states revealed that the recovery curves were similar OFF meds/OFF stim owing to faster recovery in PD seen at rest. In contrast, the effect of the motor state was different ON meds/OFF stim and ON meds/ON stim (both P < 0.05), with a nonsignificant trend OFF meds/ON stim ( P > 0.08). During a contraction, recovery curves were similar between all treatment conditions in PD and control. CONCLUSIONS: Disrupted Hoffmann reflex recovery is restored to control levels in PD patients at rest when receiving medications and/or deep brain stimulation or when engaged in voluntary contraction.

Pre-operative Limbic System Functional Connectivity Distinguishes Responders From Non-responders to Surgical Treatment for Trigeminal Neuralgia.

Background: Trigeminal neuralgia (TN) is a severe facial pain condition often requiring surgical treatment. Unfortunately, even technically successful surgery fails to achieve durable pain relief in many patients. The purpose of this study was to use resting-state functional magnetic resonance imaging (fMRI) to: (1) compare functional connectivity between limbic and accessory sensory networks in TN patients vs. healthy controls; and (2) determine if pre-operative variability in these networks can distinguish responders and non-responders to surgery for TN. Methods: We prospectively recruited 22 medically refractory classic or idiopathic TN patients undergoing surgical treatment over a 3-year period, and 19 age- and sex-matched healthy control subjects. fMRI was acquired within the month prior to surgery for all TN patients and at any time during the study period for controls. Functional connectivity analysis was restricted to six pain-relevant brain regions selected a priori: anterior cingulate cortex (ACC), posterior cingulate cortex, hippocampus, amygdala, thalamus, and insula. Two comparisons were performed: (1) TN vs. controls; and (2) responders vs. non-responders to surgical treatment for TN. Functional connectivity was assessed with a two-sample t-test, using a statistical significance threshold of p < 0.050 with false discovery rate (FDR) correction for multiple comparisons. Results: Pre-operative functional connectivity was increased in TN patients compared to controls between the right insular cortex and both the left thalamus [t (39) = 3.67, p = 0.0007] and right thalamus [t (39) = 3.22, p = 0.0026]. TN patients who were non-responders to surgery displayed increased functional connectivity between limbic structures, including between the left and right hippocampus [t (18) = 2.85, p = 0.0106], and decreased functional connectivity between the ACC and both the left amygdala [t (18) = 2.94, p = 0.0087] and right hippocampus [t (18) = 3.20, p = 0.0049]. Across all TN patients, duration of illness was negatively correlated with connectivity between the ACC and left amygdala (r 2 = 0.34, p = 0.00437) as well as the ACC and right hippocampus (r 2 = 0.21, p = 0.0318). Conclusions: TN patients show significant functional connectivity abnormalities in sensory-salience regions. However, variations in the strength of functional connectivity in limbic networks may explain why some TN patients fail to respond adequately to surgery.

DBS-Edmonton App, a Tool to Manage Patient Expectations of DBS in Parkinson Disease.

OBJECTIVE: After deep brain stimulation (DBS) for Parkinson disease (PD), patients often do not report the level of satisfaction anticipated. This misalignment can relate to patients' expectations for an invasive treatment and insufficient knowledge of DBS's effectiveness in relieving motor and nonmotor symptoms (NMS). Patient satisfaction depends on expectations and goals for treatment. We hypothesized that improving patient education with a patient-centered shared decision-making tool emphasizing autonomy would improve patient satisfaction and clinical outcome. METHODS: We developed a computer application (DBS-Edmonton app), allowing patients with PD to input their symptoms and to learn how effective DBS addresses their prioritized symptoms. Sixty-two volunteers referred for DBS used the DBS-Edmonton app. DBS-related knowledge and patient perceptions of the DBS-Edmonton app were assessed with pre- and post-use questionnaires. Fourteen of 24 patients who proceeded to DBS achieved optimization at 6 months. Perceived functional improvement was assessed and compared with 12 control patients with DBS who did not use the DBS-Edmonton app. RESULTS: All 62 volunteers considered the DBS-Edmonton app helpful and would recommend it to others. There was improved knowledge about how NMS and axial symptoms respond to DBS. Postoperatively, there was no significant difference in symptoms improvement assessed by standard scales between the groups. Volunteers who used the DBS-Edmonton app had greater satisfaction (p = 0.014). CONCLUSION: This interventional study showed that the DBS-Edmonton app improved DBS-related knowledge and patient satisfaction, independent of the objective motor outcome. It may assist patients in deciding to proceed to DBS and can be easily incorporated into practice to improve patient satisfaction post-DBS.

From vision to action: Canadian leadership in ethics and neurotechnology.

This chapter explores the complex neuroethical aspects of neurosurgery and neuromodulation in the context of Canadian healthcare and innovation, as seen through the lens of the Pan Canadian Neurotechnology Ethics Consortium (PCNEC). Highlighted are key areas of ethical focus, each with its own unique challenges: technical advances, readiness and risk, vulnerable populations, medico-legal issues, training, and research. Through an exploration of Canadian neurotechnological practice from these various clusters, we provide a critical review of progress, describe opportunities to address areas of debate, and seek to foster ethical innovation. Underpinning this comprehensive review are the fundamental principles of solution-oriented, practical neuroethics, with beneficence and justice at the core. In our view, it is a moral imperative that neurotechnological advancements include a delineation of ethical priorities for future guidelines, oversight, and interactions.

Magnetic resonance imaging analysis of human skull diploic venous anatomy.

BACKGROUND: The skull diploic venous space (DVS) represents a potential route for cerebrospinal fluid (CSF) diversion and absorption in the treatment of hydrocephalus. The goal of this study was to carry out a detailed characterization of the drainage pattern of the DVS of the skull using high-resolution MRI, especially the diploic veins draining to the lacunae laterales (LLs) since the LLs constitute an important channel for the CSF to access the superior sagittal sinus and subsequently the systemic circulation. The objective was to identify those skull regions optimally suited for an intraosseous CSF diversion system. METHODS: High-resolution, T1-weighted MRI scans from 20 adult and 16 pediatric subjects were selected for analysis. Skulls were divided into four regions, that is, frontal, parietal, temporal, and occipital. On each scan, a trained observer counted all diploic veins in every skull region. Each diploic vein was also followed to determine its final drainage pathway (i.e., dural venous sinus, dural vein, LL, or indeterminate). RESULTS: In the adult age group, the frontal and occipital skull regions showed the highest number of diploic veins. However, the highest number of draining diploic veins connecting to the lacunae lateralis was found in the frontal and parietal skull region, just anterior and just posterior to the coronal suture. In the pediatric age group, the parietal skull region, just posterior to the coronal suture, showed the highest overall number of diploic veins and also the highest number of draining diploic veins connecting to the LL. CONCLUSION: This study suggested that diploic venous density across the skull varies with age, with more parietal diploic veins in the pediatric age range, and more occipital and frontal diploic veins in adults. If the DVS is ultimately used for CSF diversion, our anatomical data point to optimal sites for the insertion of specially designed intraosseous infusion devices for the treatment of hydrocephalus. Likely the optimal sites for CSF diversion would be the parietal region just posterior to the coronal suture in children, and in adults, frontal and/or parietal just anterior or just posterior to the coronal suture.

The thalamus in trigeminal neuralgia: structural and metabolic abnormalities, and influence on surgical response.

BACKGROUND: Medically-refractory trigeminal neuralgia (TN) can be treated successfully with operative intervention, but a significant proportion of patients are non-responders despite undergoing technically successful surgery. The thalamus is a key component of the trigeminal sensory pathway involved in transmitting facial pain, but the role of the thalamus in TN, and its influence on durability of pain relief after TN surgery, are relatively understudied. We aimed to test the hypothesis that variations in thalamic structure and metabolism are related to surgical non-response in TN. METHODS: We performed a longitudinal, peri-operative neuroimaging study of the thalamus in medically-refractory TN patients undergoing microvascular decompression or percutaneous balloon compression rhizotomy. Patients underwent structural MRI and MR spectroscopy scans pre-operatively and at 1-week following surgery, and were classified as responders or non-responders based on 1-year post-operative pain outcome. Thalamus volume, shape, and metabolite concentration (choline/creatine [Cho/Cr] and N-acetylaspartate/creatine [NAA/Cr]) were evaluated at baseline and 1-week, and compared between responders, non-responders, and healthy controls. RESULTS: Twenty healthy controls and 23 patients with medically-refractory TN treated surgically (17 responders, 6 non-responders) were included. Pre-operatively, TN patients as a group showed significantly larger thalamus volume contralateral to the side of facial pain. However, vertex-wise shape analysis showed significant contralateral thalamus volume reduction in non-responders compared to responders in an axially-oriented band spanning the outer thalamic circumference (peak p = 0.019). Further, while pre-operative thalamic metabolite concentrations did not differ between responders and non-responders, as early as 1-week after surgery, long-term non-responders showed a distinct decrease in contralateral thalamic Cho/Cr and NAA/Cr, irrespective of surgery type, which was not observed in responders. CONCLUSIONS: Atrophy of the contralateral thalamus is a consistent feature across patients with medically-refractory TN. Regional alterations in preoperative thalamic structure, and very early post-operative metabolic changes in the thalamus, both appear to influence the durability of pain relief after TN surgery.

MRI Texture Analysis Reveals Brain Abnormalities in Medically Refractory Trigeminal Neuralgia.

Background: Several neuroimaging studies report structural alterations of the trigeminal nerve in trigeminal neuralgia (TN). Less attention has been paid to structural brain changes occurring in TN, even though such changes can influence the development and response to treatment of other headache and chronic pain conditions. The purpose of this study was to apply a novel neuroimaging technique-texture analysis-to identify structural brain differences between classical TN patients and healthy subjects. Methods: We prospectively recruited 14 medically refractory classical TN patients and 20 healthy subjects. 3-Tesla T1-weighted brain MRI scans were acquired in all participants. Three texture features (autocorrelation, contrast, energy) were calculated within four a priori brain regions of interest (anterior cingulate, insula, thalamus, brainstem). Voxel-wise analysis was used to identify clusters of texture difference between TN patients and healthy subjects within regions of interest (p < 0.001, cluster size >20 voxels). Median raw texture values within clusters were also compared between groups, and further used to differentiate TN patients from healthy subjects (receiver-operator characteristic curve analysis). Median raw texture values were correlated with pain severity (visual analog scale, 1-100) and illness duration. Results: Several clusters of texture difference were observed between TN patients and healthy subjects: right-sided TN patients showed reduced autocorrelation in the left brainstem, increased contrast in the left brainstem and right anterior insula, and reduced energy in right and left anterior cingulate, right midbrain, and left brainstem. Within-cluster median raw texture values also differed between TN patients and healthy subjects: TN patients could be segregated from healthy subjects using brainstem autocorrelation (p = 0.0040, AUC = 0.84, sensitivity = 89%, specificity = 70%), anterior insula contrast (p = 0.0002, AUC = 0.92, sensitivity = 78%, specificity = 100%), and anterior cingulate energy (p = 0.0004, AUC = 0.92, sensitivity = 78%, specificity = 100%). Additionally, anterior insula contrast and duration of TN were inversely correlated (p = 0.030, Spearman r = -0.73). Conclusions: Texture analysis reveals distinct brain abnormalities in TN, which relate to clinical features such as duration of illness. These findings further implicate structural brain changes in the development and maintenance of TN.

Effects of Deep Brain Stimulation and Dopaminergic Medication on Excitatory and Inhibitory Spinal Pathways in Parkinson Disease.

PURPOSE: Abnormal activity within the corticospinal system is believed to contribute to the motor dysfunction associated with Parkinson disease. However, the effect of treatment for parkinsonian motor symptoms on dysfunctional descending input to the motor neuron pool remains unclear. METHODS: We recruited nine patients with PD treated with deep brain stimulation and examined the time course of interaction between a conditioning pulse from transcranial magnetic stimulation and the soleus H-reflex. Patients with Parkinson disease were examined under four treatment conditions and compared with 10 age-matched control subjects. RESULTS: In healthy controls, transcranial magnetic stimulation conditioning led to early inhibition of the H-reflex (76.2% ± 6.3%) at a condition-test interval of -2 ms. This early inhibition was absent when patients were OFF medication/OFF stimulation (132.5% ± 20.4%; P > 0.05) but was maximally restored toward control levels ON medication/ON stimulation (80.3% ± 7.0%). Of note, early inhibition ON medication/ON stimulation tended to be stronger than when medication (85.4% ± 5.9%) or deep brain stimulation (95.7% ± 9.4%) were applied separately. Late facilitation was observed in controls at condition-test intervals ≥5 ms but was significantly reduced (by 50% to 80% of controls) in Parkinson disease OFF stimulation at condition-test intervals ≥15 ms. The late facilitation was akin to control subjects when patients were ON stimulation. CONCLUSIONS: The present pilot study demonstrates that the recruitment of early inhibition and late facilitation is disrupted in untreated Parkinson disease and that medication and deep brain stimulation may act together to normalize supraspinal drive to the motor neuron pool.

High spatial resolution nerve-specific DTI protocol outperforms whole-brain DTI protocol for imaging the trigeminal nerve in healthy individuals.

Diffusion tensor imaging (DTI) can provide markers of axonal micro-structure of the trigeminal nerve (cranial nerve five [CNV]), which may be affected in trigeminal neuralgia (TN) and other disorders. Previous attempts to image CNV have used low spatial resolution DTI protocols designed for whole-brain acquisition that are susceptible to errors from partial volume effects, particularly with adjacent cerebrospinal fluid (CSF). The purpose of this study was to develop a nerve-specific DTI protocol in healthy subjects that provides more accurate CNV tractography and diffusion quantification than whole-brain protocols. Four DTI protocols were compared in five healthy individuals (age 22-45 years, three males) on a 3 T Siemens Prisma MRI scanner: two newly developed nerve-specific high resolution (1.2 x 1.2 x 1.2 = 1.7 mm3 ) DTI protocols without (3.5 minutes) and with CSF suppression (fluid-attenuated inversion recovery [FLAIR]; 7.5 minutes) with limited slice-coverage, and two typical whole-brain protocols with either isotropic (2 x 2 x 2 = 8 mm3 ) or thicker slice anisotropic (1.9 x 1.9 x 3 = 10.8 mm3 ) voxels. Deterministic tractography was used to identify the CNV and quantify bilateral fractional anisotropy (FA), and mean (MD), axial (AD) and radial diffusivity (RD). CNV volume was determined by manual tracing on T1-weighted images. High spatial resolution nerve-specific protocols yielded better delineation of CNV, with less distortions and blurring, and markedly different diffusion parameters (42% higher FA, 35% lower MD, 27% lower RD and 43% lower AD) compared with the two lower resolution whole-brain protocols. The anisotropic whole-brain protocol showed a positive correlation between CNV FA and volume. The high resolution nerve-specific protocol with FLAIR yielded additional reductions in CNV AD and MD with a value of 1.0 x 10-3 mm2 /s, approaching that expected for healthy young adult white matter. In conclusion, high resolution nerve-specific DTI with FLAIR enhances the identification of CNV and provides more accurate quantification of diffusion compared with lower resolution whole-brain approaches.

Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson's disease: A potential biomarker for optimal electrode placement.

BACKGROUND: Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson's Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response. OBJECTIVE: We explored whether recovery of the H-reflex-an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD-could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation. METHODS: Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities. RESULTS: Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization. CONCLUSION: H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.

Characterizing the effect of low intensity transcranial magnetic stimulation on the soleus H-reflex at rest.

Modulation of a Hoffmann (H)-reflex following transcranial magnetic stimulation (TMS) has been used to assess the nature of signals transmitted from cortical centers to lower motor neurons. Further characterizing the recruitment and time-course of the TMS-induced effect onto the soleus H-reflex adds to the discussion of these pathways and may improve its utility in clinical studies. In 10 healthy controls, TMS was used to condition the soleus H-reflex using TMS intensities from 65 to 110% of the resting motor threshold (RMT). Early facilitation [- 5 to - 3 ms condition-test (C-T) interval] was evident when TMS was 110% of RMT (P < 0.05). By comparison, late facilitation (+ 10 to + 20 ms C-T interval) was several times larger and observed over a wider range of TMS intensities, including 65-110% of RMT. The early inhibition (- 3 to - 1 ms C-T interval) had a low TMS threshold and was elicited over a wide range of intensity from 65% to 95% of RMT (all P < 0.05). A second inhibitory phase was seen ~ 4 ms later (+ 1 to + 4 ms C-T intervals) and was only observed for a TMS intensity of 95% of RMT (P < 0.05). The present findings reaffirm that subthreshold TMS strongly modulates soleus motor neurons and demonstrates that distinct pathways can be selectively probed at discrete C-T intervals when using specific TMS intensities.

Association between Graduate Degrees and Publication Productivity in Academic Neurosurgery.

OBJECT: Many neurosurgeons pursue graduate degrees as part of their training. In some jurisdictions, graduate degrees are considered a necessary condition of employment in academic neurosurgery. However, the relationship between possession of a graduate degree and eventual research productivity is not well established. We used bibliometric methods to analyze publications from academic Canadian neurosurgeons, with an emphasis on level of graduate training. METHODS: All neurosurgeons holding academic appointments at Canadian institutions from 2012-2016 were included. Over that time frame, Scopus was used to quantify the number of papers, number of citations, 5-year h-index and 5-year r-index, CiteScore, authorship position, and paper type (clinical or basic science). Publication output was compared between neurosurgeons grouped as MD-only, MD-Masters, or MD-PhD. RESULTS: In total, 2557 abstracts from 131 Canadian neurosurgeons were analyzed. We found that MD-Masters neurosurgeons published significantly more total papers, clinical papers, and first/last author papers than MD-only neurosurgeons. MD-PhD neurosurgeons had the same findings, in addition to more basic science papers, in journals with a higher CiteScore, 5-year h-index, and 5-year r-index than both other groups. These results were preserved even with significant outliers removed. There was no difference if graduate degrees were obtained before or after starting residency. There was no correlation with career length and number of recent papers published. CONCLUSION: The attainment of a graduate degree has an important association with future publication productivity for academic neurosurgeons. These data should be useful for hiring committees considering the value of graduate degrees from applicants for positions in academic neurosurgery.

Neuroanatomical predictors of response to subcallosal cingulate deep brain stimulation for treatment-resistant depression

Background: Deep brain stimulation targeting the subcallosal cingulate gyrus (SCG DBS) improves the symptoms of treatment-resistant depression in some patients, but not in others. We hypothesized that there are pre-existing structural brain differences between responders and nonresponders to SCG DBS, detectable using structural MRI. Methods: We studied preoperative, T1-weighted MRI scans of 27 patients treated with SCG DBS from 2003 to 2011. Responders (n = 15) were patients with a >50% improvement in Hamilton Rating Scale for Depression score following 12 months of SCG DBS. Preoperative subcallosal cingulate gyrus grey matter volume was obtained using manual segmentation by a trained observer blinded to patient identity. Volumes of hippocampus, thalamus, amygdala, whole-brain cortical grey matter and white matter volume were obtained using automated techniques. Results: Preoperative subcallosal cingulate gyrus, thalamic and amygdalar volumes were significantly larger in patients who went on to respond to SCG-DBS. Hippocampal volume did not differ between groups. Cortical grey matter volume was significantly smaller in responders, and cortical grey matter:white matter ratio distinguished between responders and nonresponders with high sensitivity and specificity. Limitations: Normalization by intracranial volume nullified some between-group differences in volumetric measures. Conclusion: There are structural brain differences between patients with treatment-resistant depression who respond to SCG DBS and those who do not. Specifically, the structural integrity of the subcallosal cingulate gyrus target region and its connected subcortical areas, and variations in cortical volume across the entire brain, appear to be important determinants of response. Structural MRI shows promise as a biomarker in deep brain stimulation for depression, and may play a role in refining patient selection for future trials.

Hippocampal and trigeminal nerve volume predict outcome of surgical treatment for trigeminal neuralgia.

BACKGROUND: Many medically-refractory trigeminal neuralgia patients are non-responders to surgical treatment. Few studies have explored how trigeminal nerve characteristics relate to surgical outcome, and none have investigated the relationship between subcortical brain structure and treatment outcomes. METHODS: We retrospectively studied trigeminal neuralgia patients undergoing surgical treatment with microvascular decompression. Preoperative magnetic resonance imaging was used for manual tracing of trigeminal nerves and automated segmentation of hippocampus, amygdala, and thalamus. Nerve and subcortical structure volumes were compared between responders and non-responders and assessed for ability to predict postoperative pain outcome. RESULTS: In all, 359 trigeminal neuralgia patients treated surgically from 2005-2018 were identified. A total of 34 patients met the inclusion criteria (32 with classic and two with idiopathic trigeminal neuralgia). Across all patients, thalamus volume was reduced ipsilateral compared to contralateral to the side of pain. Between responders and non-responders, non-responders exhibited larger contralateral trigeminal nerve volume, and larger ipsilateral and contralateral hippocampus volume. Through receiver-operator characteristic curve analyses, contralateral hippocampus volume correctly classified treatment outcome in 82% of cases (91% sensitive, 78% specific, p = 0.008), and contralateral nerve volume correctly classified 81% of cases (91% sensitive, 75% specific, p < 0.001). Binomial logistic regression analysis showed that contralateral hippocampus and contralateral nerve volumes together classified outcome with 84% accuracy (Nagelkerke R2 = 65.1). CONCLUSION: Preoperative hippocampal and trigeminal nerve volume, measured on standard clinical magnetic resonance images, may predict early non-response to surgical treatment for trigeminal neuralgia. Treatment resistance in medically refractory trigeminal neuralgia may depend on the structural features of both the trigeminal nerve and structures involved in limbic components of chronic pain.

Predicting high-intensity focused ultrasound thalamotomy lesions using 2D magnetic resonance thermometry and 3D Gaussian modeling.

PURPOSE: To develop a method of using two-dimensional (2D) magnetic resonance thermometry, and three-dimensional (3D) Gaussian modeling to predict the volume, shape, and location of 1 day postoperative T1w high-intensity focused ultrasound lesions in medication refractory tremor patients; thereby facilitating a better comprehension of thermal damage thresholds, which can be utilized to reduce adverse events, and improve patient outcome. METHODS: Fifteen patients underwent magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy, which was performed at our center using an InSightec ExAblate 4000 system (Haifa, Israel), and guided by magnetic resonance imaging using a 3 T Discovery 750 (General Electric Healthcare, Waukesha, WI, USA). For treatment monitoring, 2D MR thermometry (temperature sensitivity: -0.00909 ppm/°C, bandwidth: 279 Hz/pixel) was performed in multiple orthogonal planes (sagittal, coronal, and axial) intraoperatively. These images were temporally filtered using a general linear model approach to reduce noise. Temporal volumes of filtered temperature maps with a peak temperature ≥ 47°C were aligned and fitted with a 3D Gaussian to create a canonical heating model. We then fitted the filtered 2D temperature maps with a 3D Gaussian, and used the relationships derived from the 3D heating model to estimate the 3D temperature distribution. These temperature distributions were converted into thermal dose distributions and accumulated across time to create an accumulated thermal dose (ATD) profile. Thresholded ATD profiles were then correlated with manually traced T1-weighted 1 day postoperative lesion volumes across patients, and linear regression slopes were plotted against varying ATD thresholds. Additionally, the Dice-Sørensen coefficient (DSC) was calculated to quantify the volumetric overlap between predicted, and actual lesions. RESULTS: On average, 18.1 (standard deviation (SD): ±4.6, range: 10-29) sonications were performed with an average peak temperature achieved of 62.4°C (SD: ±2.4, range: 58.2-67.7). An ATD threshold of 35.8 CEM43 was found to give a unity linear regression slope; this corresponded to an average DSC of 0.689 (SD: ±0.090, range: 0.476-0.815). CONCLUSIONS: Using multiplanar 2D MR thermometry and 3D Gaussian modeling, we were able to achieve very good (DSC = 0.689) predictions of T1w 1 day postoperative lesion volume, shape and location at an ATD threshold of approximately 36 CEM43. Furthermore, this method has the potential to be used in clinical evaluations to further elucidate the relationship between thermal damage and clinical outcome. Accurate 3D lesion prediction will facilitate improved clinical decision making in future MRgFUS thalamotomies.