Surgical considerations for spinal epidural hematoma evacuation in the setting of blue rubber bleb nevus syndrome in a child.

Blue rubber bleb nevus syndrome (BRBNS) is a rare condition that presents with venous malformation blebs throughout the body, most commonly on the skin and gastrointestinal tract. There have only been a limited number of reports of benign BRBNS lesions involving the spine in children, which were detected after chronic symptomatology. We herein present a unique case of a ruptured BRBNS venous malformation into the epidural space of the lumbar spine in a child presenting with acute neurologic deficit and discuss the relevant surgical considerations for operating in the setting of BRBNS.

Connectivity-based thalamus parcellation and surgical targeting of somatosensory subnuclei.

OBJECTIVE: The anatomy of the posterolateral thalamus varies substantially between individuals, presenting a challenge for surgical targeting. Patient-specific, connectivity-based parcellation of the thalamus may effectively approximate the ventrocaudal nucleus (Vc). This remains to be robustly validated or assessed as a method to guide surgical targeting. The authors assessed the validity of connectivity-based parcellation for targeting the Vc and its potential for improving clinical outcomes of pain surgery. METHODS: A cohort of 19 patients with regional, chronic neuropathic pain underwent preoperative structural and diffusion MRI, then progressed to deep brain stimulation targeting the Vc based on traditional atlas coordinates. Surgical thalami were retrospectively segmented and then parcellated based on tractography estimates of thalamocortical connectivity. The location of each patient's electrode array was analyzed with respect to their primary somatosensory cortex (S1) parcel and compared across patients with reference to the thalamic homunculus. RESULTS: Ten patients achieved long-term pain relief. Sixty-one percent of an average array (interquartile range 42%-74%) was located in the S1 parcel. In patients who achieved long-term benefit from surgery, array location in the individually generated S1 parcels was medial for face pain, centromedial for arm pain, and centrolateral for leg pain. Patients who did not benefit from surgery did not follow this pattern. Standard stereotactic coordinates of electrode locations diverged from this pattern. CONCLUSIONS: Connectivity-based parcellation of the thalamus appears to be a reliable method for segmenting the Vc. Identifying the Vc in this way, and targeting mediolaterally as appropriate for the region of pain, merits exploration in an effort to increase the yield of successful surgical procedures.

Paired Acute Invasive/Non-invasive Stimulation (PAINS) study: A phase I/II randomized, sham-controlled crossover trial in chronic neuropathic pain.

BACKGROUND: Dorsal root ganglion (DRG) stimulation, an invasive method of neuromodulation, and transcranial direct current stimulation (tDCS), a non-invasive method of altering cortical excitability, have both proven effective in relieving chronic pain. OBJECTIVE: We employed a randomized, sham-controlled crossover study design to investigate whether single-session tDCS would have an additive therapeutic effect alongside DRG stimulation (DRGS) in the treatment of chronic pain. METHODS: Sixteen neuropathic pain patients who were previously implanted with DRG stimulators were recruited. Baseline pain scores were established with DRGS-OFF. Pain scores were then recorded with DRGS-ON, after paired sham tDCS stimulation, and after paired active anodal tDCS (a-tDCS) stimulation. For active tDCS, patients were randomized to 'MEG (magnetoencephalography) localized' tDCS or contralateral motor cortex (M1) tDCS for 30 min. EEG recordings and evaluations of tDCS adverse effects were also collected. RESULTS: All participants reported the interventions to be tolerable with no significant adverse effects during the session. Paired DRGS/active tDCS resulted in a significant reduction in pain scores compared to paired DRGS-ON/sham tDCS or DRGS alone. There was no difference in the additive effect of M1 vs. MEG-localized tDCS. Significant augmentation of beta activity was observed between DRGS-OFF and DRGS-ON conditions, as well as between paired DRGS-ON/sham tDCS and paired DRGS-ON/active tDCS. CONCLUSION: Our results indicate that a single session of tDCS alongside DRGS is safe and can significantly reduce pain acutely in neuropathic pain patients. Paired invasive/non-invasive neuromodulation is a promising new treatment strategy for pain management and should be evaluated further to assess long-term benefits.

Supraspinal Effects of Dorsal Root Ganglion Stimulation in Chronic Pain Patients.

OBJECTIVES: Dorsal root ganglion stimulation (DRGS) has become a popular neuromodulatory treatment for neuropathic pain. We used magnetoencephalography (MEG) to investigate potential biomarkers of pain and pain relief, based on the differences in power spectral density (PSD) during varying degrees of pain and how these oscillations change during DRGS-mediated pain relief. MATERIALS AND METHODS: Thirteen chronic pain patients with implanted dorsal root ganglion stimulators were included in the MEG analysis. MEG Recordings were performed at rest while the stimulator was turned ON or OFF. Numerical rating scale (NRS) scores were also recorded before and after DRGS was turned OFF and ON. Power spectral and source localization analyses were then performed on preprocessed MEG recordings. RESULTS: With DRGS-OFF, patients in severe pain had significantly increased cortical theta (4-7 Hz) power and decreased cortical alpha (7-13 Hz) power compared to patients reporting less pain. This shift in power toward lower frequencies was contrasted by a shift toward the higher frequency power spectrum (low beta 13-20 Hz activity) during DRGS-mediated pain relief. A significant correlation was found between the increase in low beta activity and the degree of reported pain relief. CONCLUSION: Our results demonstrate increased low-frequency power spectral activity in chronic pain patients in the absence of stimulation which shifts toward higher frequency power spectrum activity in response to therapeutic DRGS. These cortical changes in response to DRGS provide support for the use of neuroimaging in the search for potential biomarkers of pain.

Tractography patterns of pedunculopontine nucleus deep brain stimulation.

Deep brain stimulation of the pedunculopontine nucleus is a promising surgical procedure for the treatment of Parkinsonian gait and balance dysfunction. It has, however, produced mixed clinical results that are poorly understood. We used tractography with the aim to rationalise this heterogeneity. A cohort of eight patients with postural instability and gait disturbance (Parkinson's disease subtype) underwent pre-operative structural and diffusion MRI, then progressed to deep brain stimulation targeting the pedunculopontine nucleus. Pre-operative and follow-up assessments were carried out using the Gait and Falls Questionnaire, and Freezing of Gait Questionnaire. Probabilistic diffusion tensor tractography was carried out between the stimulating electrodes and both cortical and cerebellar regions of a priori interest. Cortical surface reconstructions were carried out to measure cortical thickness in relevant areas. Structural connectivity between stimulating electrode and precentral gyrus (r = 0.81, p = 0.01), Brodmann areas 1 (r = 0.78, p = 0.02) and 2 (r = 0.76, p = 0.03) were correlated with clinical improvement. A negative correlation was also observed for the superior cerebellar peduncle (r = -0.76, p = 0.03). Lower cortical thickness of the left parietal lobe and bilateral premotor cortices were associated with greater pre-operative severity of symptoms. Both motor and sensory structural connectivity of the stimulated surgical target characterises the clinical benefit, or lack thereof, from surgery. In what is a challenging region of brainstem to effectively target, these results provide insights into how this can be better achieved. The mechanisms of action are likely to have both motor and sensory components, commensurate with the probable nature of the underlying dysfunction.

Invasive Electrical Neuromodulation for the Treatment of Painful Diabetic Neuropathy: Systematic Review and Meta-Analysis.

OBJECTIVES: Neuromodulation is a treatment option for people suffering from painful diabetic neuropathy (PDN) unresponsive to conventional pharmacotherapy. We systematically examined the pain outcomes of patients with PDN receiving any type of invasive neuromodulation for treatment of neuropathic pain. MATERIALS AND METHODS: MEDLINE and Embase were searched through 10 January 2020, without language restriction. All study types were included. Two reviewers independently screened publications and extracted data. Quantitative meta-analysis was performed with pain scores converted to a standard 100-point scale. Randomized controlled trial (RCT) scores were pooled using the inverse variance method and expressed as mean differences. RESULTS: RCTs of tonic spinal cord stimulation (t-SCS) showed greater pain improvement than best medical therapy at six months (intention-to-treat: 38/100, 95% CI: 29-47). By per-protocol analysis, case series of t-SCS and dorsal root ganglion stimulation (DRGS) showed improvement by 56 (95% CI: 39-73) and 55 (22-87), respectively, at 12 months. For t-SCS, the rate of failing a therapeutic stimulation trial was 16%, the risk of infection was 4%, and the rate of lead problems requiring surgery to resolve was 4% per year of follow-up. High-frequency SCS and burst SCS both showed efficacy, with few patients studied. CONCLUSION: Efficacious, lasting and safe surgical pain management options are available to diabetic patients suffering from PDN. Tonic-SCS is the established standard of treatment; however, other SCS paradigms and DRGS are emerging as promising treatments offering comparable pain benefits, but with few cases published to date. Randomized controlled trials are ongoing to assess their relative merits.

Gamma knife radiosurgery for uveal melanomas and metastases: a systematic review and meta-analysis.

BACKGROUND: Gamma knife radiosurgery is regarded as the gold-standard stereotactic radiosurgery modality for the treatment of intracranial tumours, and its use has been expanded for the treatment of intraocular malignancies. The aim of this study was to systematically evaluate the efficacy, outcomes, and complications of gamma knife radiosurgery for uveal melanomas and metastases. METHODS: We did a systematic review and meta-analysis to aggregate the clinical outcomes of patients with uveal melanomas or intraocular metastases treated primarily with gamma knife radiosurgery. We searched MEDLINE and Embase for studies published between Sept 1, 1960, and Feb 1, 2020, reporting the use of gamma knife radiosurgery as primary treatment for uveal melanoma or uveal metastases. The search was restricted to clinical studies and relevant grey literature published in English. Studies reporting treatment of benign tumours, extraocular tumours, or other forms of stereotactic radiosurgery were excluded to reduce heterogeneity. No restrictions were placed on participant criteria. Local tumour control and tumour regression were extracted as the primary outcomes and analysed via a random-effects meta-analysis of proportions using the DerSimonian and Laird method with a Freeman-Tukey double arcsine transformation. This study is registered with PROSPERO, CRD42019148165. FINDINGS: Our search returned 454 studies, of which 109 were assessed for full-text eligibility. 52 studies, reporting on 1010 patients with uveal melanoma and 34 intraocular metastases, were eligible for systematic review. 28 studies were included in the meta-analysis. 840 of 898 patients (0·96, 95% CI 0·94-0·97; I2=16%) from 19 studies had local control, and 378 of 478 patients (0·81, 0·70-0·90; I2=83%) from 16 studies experienced tumour regression. INTERPRETATION: Gamma knife radiosurgery is an efficacious primary method of treating uveal melanomas and intraocular metastases, with reliable tumour control rates. Randomised controlled trials should further evaluate the safety and efficacy of gamma knife radiosurgery in this setting. FUNDING: The Rhodes Trust and the Howard Brain Sciences Foundation.

Global Neurosurgery Education in United States Residency Programs.

BACKGROUND: Global neurosurgery encompasses the social and surgical practices that effect the neurologic health of vulnerable and underserved populations in domestic and international resource-limited settings. Formal academic engagement in global neurosurgery is limited in residency programs. Here we explore the current status of global neurosurgery education in residency programs across the United States. METHODS: We contacted 115 Accreditation Council for Graduate Medical Education-accredited residency programs in the United States to complete an 8-question electronic survey on global neurosurgery education. Questions were framed with binary "yes" or "no" answers to indicate presence of a global health activity. Respondents provided additional information if desired. Global education activity was categorized based on the number of resources attributed to global health activities: low (0-2), moderate (3-5), or high (6-8). RESULTS: Thirty-four residency programs completed the survey (29.6%). The majority of respondents reported offering funding for research and educational opportunities in global neurosurgery (n = 22). Programs tended to support global neurosurgery conferences (n = 20), periodic dedicated lectures (n = 15), and rotations in resource-constrained or marginalized communities domestically or abroad (n = 15). Some programs offer continuity clinics in marginalized settings (n = 10), supplementary reading material (n = 8), core curricula (n = 6), or a designated residency track in global neurosurgery (n = 3). The majority of residency programs had low-level engagement in global neurosurgery (n = 18), with only 3 programs having high levels of engagement. CONCLUSIONS: Formal global neurosurgery training is limited within US residency programs. With rising trends in the neurosurgical disease burden globally, it may benefit residency programs to develop training paths to equip the next generation of neurosurgeons to address such needs.

Pain-Induced Beta Activity in the Subthalamic Nucleus of Parkinson's Disease.

BACKGROUND: The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) in Parkinson's disease (PD) and is believed to serve a role in sensorimotor integration. In addition to therapeutic neuromodulation, DBS facilitates the recording of local-field potentials (LFPs) in order to further understand the neurophysiological basis of disease. The capacity to wirelessly transmit these signals in real time has overcome the obstacle of externalization of electrodes during LFP recordings. OBJECTIVE: Using the G102RS device (PINS Medical, China), we investigated the LFP changes in response to mechanical pain stimulation to further elucidate the representation of pain sensation in the basal ganglia. METHODS: LFPs from 2 patients who had undergone bilateral STN-DBS were wirelessly recorded during no stimulation, low-frequency stimulation (60 and 90 Hz), and high-frequency stimulation (130 and 150 Hz) while introducing painful and nonpainful stimuli. Power spectral analysis was conducted to compare the changes in ß frequency (13-30 Hz) during each stimulus. RESULTS: During painful stimuli, STN power spectra (n = 4) revealed a significant increase in ß activity compared to non-painful and no-stimulus epochs. Both low- and high-frequency stimulation produced a significant decrease in pain-related ß activity. CONCLUSION: These 2 cases have demonstrated the potential for acute noxious stimuli to exacerbate pathologic ß oscillatory activity in the STN. Our findings represent novel evidence of the neurophysiologic representation of pain in the STN of PD patients.

Dorsal Root Ganglion Stimulation Modulates Cortical Gamma Activity in the Cognitive Dimension of Chronic Pain.

A cognitive task, the n-back task, was used to interrogate the cognitive dimension of pain in patients with implanted dorsal root ganglion stimulators (DRGS). Magnetoencephalography (MEG) signals from thirteen patients with implanted DRGS were recorded at rest and while performing the n-back task at three increasing working memory loads with DRGS-OFF and the task repeated with DRGS-ON. MEG recordings were pre-processed, then power spectral analysis and source localization were conducted. DRGS resulted in a significant reduction in reported pain scores (mean 23%, p = 0.001) and gamma oscillatory activity (p = 0.036) during task performance. DRGS-induced pain relief also resulted in a significantly reduced reaction time during high working memory load (p = 0.011). A significant increase in average gamma power was observed during task performance compared to the resting state. However, patients who reported exacerbations of pain demonstrated a significantly elevated gamma power (F(3,80) = 65.011612, p < 0.001, adjusted p-value = 0.01), compared to those who reported pain relief during the task. Our findings demonstrate that gamma oscillatory activity is differentially modulated by cognitive load in the presence of pain, and this activity is predominantly localized to the prefrontal and anterior cingulate cortices in a chronic pain cohort.

Multitarget deep brain stimulation for clinically complex movement disorders.

Deep brain stimulation (DBS) of single-target nuclei has produced remarkable functional outcomes in a number of movement disorders such as Parkinson's disease, essential tremor, and dystonia. While these benefits are well established, DBS efficacy and strategy for unusual, unclassified movement disorder syndromes is less clear. A strategy of dual pallidal and thalamic electrode placement is a rational approach in such cases where there is profound, medically refractory functional impairment. The authors report a series of such cases: midbrain cavernoma hemorrhage with olivary hypertrophy, spinocerebellar ataxia-like disorder of probable genetic origin, Holmes tremor secondary to brainstem stroke, and hemiballismus due to traumatic thalamic hemorrhage, all treated by dual pallidal and thalamic DBS. All patients demonstrated robust benefit from DBS, maintained in long-term follow-up. This series demonstrates the flexibility and efficacy, but also the limitations, of dual thalamo-pallidal stimulation for managing axial and limb symptoms of tremors, dystonia, chorea, and hemiballismus in patients with complex movement disorders.

Insula stroke: the weird and the worrisome.

Infarction of the insula is a common scenario with large tissue-volume strokes in the middle cerebral artery territory. Considered to be part of the central autonomic network, infarction of this region is associated with autonomic disturbances, in particular cardiovascular dysregulation. Risk of aspiration following stroke is also associated with involvement of the insula, consistent with its purported participation in complex functions of the mouth and pharynx. Strokes restricted to the insula are rare and present with a broad range of symptoms that offer a window of insight into the diverse functionality of the insular cortex. Chemosensory, autonomic, vestibular, auditory, somatosensory, language and oropharyngeal functional deficits are all recognised, among others. Long-term sequelae are unknown but profound symptoms, such as hemiparesis, are usually transient. Understanding the patterns of dysfunction highlighted provides the basis for future strategies to optimise stroke management on the discovery of insula involvement.