Reciprocal changes in sagittal spinal alignment after L5-S1 anterior lumbar interbody fusion.

OBJECTIVE: Degenerative diseases of the lumbar spine decrease lumbar lordosis (LL). Anterior lumbar interbody fusion (ALIF) at the L5-S1 disc space improves segmental lordosis, LL, and sagittal balance. This study investigated reciprocal changes in spinopelvic alignment after L5-S1 ALIF. METHODS: A retrospective chart review identified patients who underwent L5-S1 ALIF with or without posterior fixation at a single institution (November 1, 2016-October 1, 2021). Changes in pelvic tilt, sacral slope, proximal LL (L1-L4), distal LL (L4-S1), total LL (L1-S1), segmental lordosis, pelvic incidence-LL mismatch, thoracic kyphosis, cervical lordosis, and sagittal vertical axis were measured on preoperative and postoperative radiographs. RESULTS: Forty-eight patients were identified. Immediate postoperative radiographs were obtained at a mean (SD) of 17 (20) days after surgery; delayed radiographs were obtained 184 (82) days after surgery. After surgery, patients had significantly decreased pelvic tilt (15.71° [7.25°] vs 17.52° [7.67°], p=0.003) and proximal LL (11.86° [10.67°] vs 16.03° [10.45°], p<0.001) and increased sacral slope (39.49° [9.27°] vs 36.31° [10.39°], p<0.001), LL (55.35° [13.15°] vs 51.63° [13.38°], p=0.001), and distal LL (43.17° [9.33°] vs 35.80° [8.02°], p<0.001). Segmental lordosis increased significantly at L5-S1 and decreased significantly at L2-3, L3-4, and L4-5. Lordosis distribution index increased from 72.55 (19.53) to 81.38 (22.83) (p<0.001). CONCLUSIONS: L5-S1 ALIF was associated with increased L5-S1 segmental lordosis accompanied by pelvic anteversion and a reciprocal decrease in proximal lumbar lordosis. These changes may represent a reversal of compensatory mechanisms, suggesting an overall relaxation of spinopelvic alignment after L5-S1 ALIF.

Radiographic and Clinical Outcomes After Stand-Alone Anterior Lumbar Interbody Fusion for Symptomatic L5-S1 Retrolisthesis.

BACKGROUND AND OBJECTIVES: Degenerative lumbar spondylolisthesis is associated with significant pain and disability. The literature on the treatment options and clinical outcomes for lumbar anterolisthesis is robust, but very few reports specifically evaluate lumbar retrolisthesis. This study investigated surgical outcomes for symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 anterior lumbar interbody fusion (ALIF). METHODS: All patients with symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 ALIF at a single institution over a 7-year period were identified. Exhaustive nonoperative management had failed for all patients. Patients with previous lumbar fusion were excluded. Preoperative and postoperative radiographic images and patient-reported outcome measures for 20 patients (14 males and 6 females; mean [SD] age, 50.3 [13.7] years) were analyzed. RESULTS: The mean (SD) follow-up was 43.0 (23.7) months (range, 12.1-102.5 months). Patients experienced postoperative improvements in L5-S1 retrolisthesis (P = .048), L5-S1 disk height and angle (P < .001), L5 foraminal height (P < .001), L5-S1 lordosis (P < .001), and lumbar lordosis (P = .01). There were no significant changes in spinopelvic parameters. At the most recent follow-up, minimal clinically important differences in Oswestry Disability Index score, 36-Item Short-Form Survey (SF-36), and numerical rating scale score for leg pain were achieved in 11 of 20 (55%), 7 of 14 (50%), and 7 of 13 (54%) patients, respectively. All patients demonstrated fusion with no graft subsidence at up to 32 months. No patient experienced intraoperative complications, was readmitted, or required a subsequent posterior decompression or fusion because of refractory symptoms. CONCLUSION: In our cohort, stand-alone L5-S1 ALIF was associated with radiographic and clinical improvement in patients with symptomatic L5-S1 retrolisthesis.

Microscale electrophysiological functional connectivity in human cortico-basal ganglia network.

OBJECTIVE: We investigated the electrophysiological relationships in the cortico-basal ganglia network on a sub-centimeter scale to increase our understanding of neural functional relationships in Parkinson's disease (PD). METHODS: Data was intraoperatively recorded from 2 sources in the human brain-a microelectrode in the subthalamic nucleus (STN) and a micro-electrocorticography grid on the motor association cortex-during bilateral deep brain stimulation (DBS) electrode placement. STN neurons and local field potential (LFP) were defined as functionally connected when the 99.7% confidence intervals of the action potential (AP)-aligned average LFP and control did not overlap. RESULTS: APs from STN neurons were functionally connected to the STN LFP for 18/46 STN neurons. This functional connection was observed between STN neuron APs and cortical LFP for 25/46 STN neurons. The cortical patterns of electrophysiological functional connectivity differed for each neuron. CONCLUSIONS: A subset of single neurons in the STN exhibited functional connectivity with electrophysiological activity in the STN and at a distance with the motor association cortex surveyed on a sub-centimeter spatial scale. These connections show a per neuron differential topography on the cortex. SIGNIFICANCE: The cortico-basal ganglia circuit is organized on a sub-centimeter scale, and plays an important role in the mechanisms of PD and DBS.

Technical Feasibility of Subaxial Cervical Pedicle Screws for Distal Anchoring of Occipitocervical Fixation Constructs in the Mid-Cervical Spine: Early Clinical Experience.

Occipitocervical fixation and fusion (OCF) is performed for patients who have destabilizing traumatic injuries or pathologies affecting the complex bony and ligamentous structures of the occipitoatlantal and atlantoaxial joint structures. Distal fixation failure and pseudoarthrosis are known risks of these constructs, especially for those constructs ending in the mid-cervical spine. We present the technical feasibility of using cervical pedicle screws (CPSs) as distal fixation anchors to strengthen OCF constructs ending in the mid-cervical spine and present a case series describing our early clinical experience with this technique. We used a freehand technique to place subaxial pedicle screws in the mid-cervical spine as the distal fixation point in OCF constructs. This technique involves performing a laminotomy to provide direct visualization of the pedicle borders to safely guide freehand pedicle screw placement. Our early clinical experience with this technique is presented. Three patients received OCF constructs ending in the mid-cervical subaxial spine between C3 and C6. CPSs were placed at the distal vertebra in each construct. Stable instrumentation and arthrodesis were confirmed postoperatively in all patients. This freehand technique uses direct visualization of the pedicle to aid in safe and accurate subaxial pedicle screw placement. CPS placement is clinically feasible and increases the robustness of OCF constructs in appropriately selected patients. Larger case series are needed to further validate the safety and effectiveness of this technique.

Factors Contributing to Spinal Cord Stimulation Outcomes for Chronic Pain.

OBJECTIVE: Spinal cord stimulation (SCS) has been shown to be a safe and effective therapy for patients with chronic pain. However, some patients do not obtain or maintain adequate pain relief after SCS. The goal of this study was to identify factors that affect patient outcome with regard to SCS. MATERIALS AND METHODS: A retrospective analysis of electronic medical records at a single site was performed. Records for 181 patients who received SCS implants from 2014 through 2016 were collected with follow-up data captured up to August 2019. Patient outcome was measured by device explantation and patient benefit from the SCS. Study parameters included demographic characteristics, history of pain, SCS implant characteristics, and postimplantation events. RESULTS: An earlier diagnosis of radiculopathy was associated with an increased risk of poor benefit (relative risk [RR], 1.81; 95% CI, 1.19-2.74; p = 0.008). Postimplantation falls were associated with an increased risk of poor benefit (RR, 2.17; 95% CI, 1.48-3.17; p = 0.009). Device manufacturer was associated with both patient benefit and explantation. Device 2 was associated with a reduced risk of poor benefit (RR, 0.52; 95% CI, 0.32-0.85; p = 0.009). Device 4 was associated with an increased risk of poor benefit (RR, 1.71; 95% CI, 1.14-2.55; p = 0.02) and increased risk of device explantation (RR, 2.69; 95% CI, 1.2-6.02; p = 0.03). CONCLUSIONS: Patient outcome was associated with diagnosis, postimplantation falls, and device manufacturer. Further investigation is recommended to confirm associations through prospective studies that can more accurately quantify patient outcome over longer periods.

Central Nervous System Control of Glucose Homeostasis: A Therapeutic Target for Type 2 Diabetes?

Historically, pancreatic islet beta cells have been viewed as principal regulators of glycemia, with type 2 diabetes (T2D) resulting when insulin secretion fails to compensate for peripheral tissue insulin resistance. However, glycemia is also regulated by insulin-independent mechanisms that are dysregulated in T2D. Based on evidence supporting its role both in adaptive coupling of insulin secretion to changes in insulin sensitivity and in the regulation of insulin-independent glucose disposal, the central nervous system (CNS) has emerged as a fundamental player in glucose homeostasis. Here, we review and expand upon an integrative model wherein the CNS, together with the islet, establishes and maintains the defended level of glycemia. We discuss the implications of this model for understanding both normal glucose homeostasis and T2D pathogenesis and highlight centrally targeted therapeutic approaches with the potential to restore normoglycemia to patients with T2D.

Neurosurgical Treatments for Cancer Pain.

Cancer-related pain is a uniquely challenging entity for treating practitioners for a variety of reasons, including its often severe and medically refractory nature, the emotional and social circumstances surrounding the disease process, and the frequently associated limited life expectancy.

Electrophysiologic Mapping for Target Acquisition in Deep Brain Stimulation May Become Unnecessary in the Era of Intraoperative Imaging.

OBJECTIVE: Electrophysiologic mapping (EM) has been instrumental in advancing neuroscience and ensuring accurate lead placement for deep brain stimulation. However, EM is associated with increased operative time, expense, and potential risk. Intraoperative imaging to verify lead placement provides an opportunity to reassess the clinical role of EM. We investigated whether EM 1) provides new information that corrects suboptimal preoperative target selection by the physician or 2) simply corrects intraoperative stereotactic error, which can instead be quickly corrected with intraoperative imaging. METHODS: Deep brain stimulation lead location errors were evaluated by measuring whether repositioning leads based on EM directed the final lead placement 1) away from or 2) toward the original target. We retrospectively identified 50 patients with 61 leads that required repositioning directed by EM. The stereotactic coordinates of each lead were determined with intraoperative computed tomography. RESULTS: In 45 of 61 leads (74%), the electrophysiologically directed repositioning moved the lead toward the initial target. The mean radial errors between the preoperative plan and targeted contact coordinates before and after repositioning were 2.2 and 1.5 mm, respectively (P < 0.001). Microelectrode recording was more likely than test stimulation to direct leads toward the initial target (88% vs. 63%; P = 0.03). The nucleus targeted was associated with the likelihood of moving toward the initial target. CONCLUSIONS: Electrophysiologic mapping corrected primarily for errors in lead placement rather than providing new information regarding errors in target selection. Thus, intraoperative imaging and improvements in stereotactic techniques may reduce or even eliminate dependence on EM.

Leptin receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism.

The brain plays an essential role in driving daily rhythms of behavior and metabolism in harmony with environmental light-dark cycles. Within the brain, the dorsomedial hypothalamic nucleus (DMH) has been implicated in the integrative circadian control of feeding and energy homeostasis, but the underlying cell types are unknown. Here, we identify a role for DMH leptin receptor-expressing (DMHLepR) neurons in this integrative control. Using a viral approach, we show that silencing neurotransmission in DMHLepR neurons in adult mice not only increases body weight and adiposity but also phase-advances diurnal rhythms of feeding and metabolism into the light cycle and abolishes the normal increase in dark-cycle locomotor activity characteristic of nocturnal rodents. Finally, DMHLepR-silenced mice fail to entrain to a restrictive change in food availability. Together, these findings identify DMHLepR neurons as critical determinants of the daily time of feeding and associated metabolic rhythms.

Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats.

We recently showed that perineuronal nets (PNNs) enmesh glucoregulatory neurons in the arcuate nucleus (Arc) of the mediobasal hypothalamus (MBH)1, but whether these PNNs play a role in either the pathogenesis of type 2 diabetes (T2D) or its treatment remains unclear. Here we show that PNN abundance within the Arc is markedly reduced in the Zucker diabetic fatty (ZDF) rat model of T2D, compared with normoglycaemic rats, correlating with altered PNN-associated sulfation patterns of chondroitin sulfate glycosaminoglycans in the MBH. Each of these PNN-associated changes is reversed following a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) at a dose that induces sustained diabetes remission in male ZDF rats. Combined with previous work localizing this FGF1 effect to the Arc area2-4, our finding that enzymatic digestion of Arc PNNs markedly shortens the duration of diabetes remission following icv FGF1 injection in these animals identifies these extracellular matrix structures as previously unrecognized participants in the mechanism underlying diabetes remission induced by the central action of FGF1.

Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission.

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.

Neurosurgical Management of Cancer Facial Pain.

Facial pain occurs in approximately 80% of patients with head and neck cancers. Pain in these settings may result directly from the tumor, or indirectly as a side effect of oncological treatment of the tumor. Optimizing treatment for cancer pain of the face, therefore, involves a variety of diagnostic and treatment considerations, with the development of a successful treatment algorithm dependent on accurate diagnosis of the anatomical location of the pain, its relationship to the facial pain pathway, the type of pain being treated and, finally, patient's prognosis and preference for treatment modality. Beyond direct treatments to reduce tumor burden, a wide variety of neuro-ablative and neuro-augmentative approaches are available that may be tailored to a patient's specific pain syndrome and individual clinical context, taking into account the patient's treatment goals, life expectancy, other cancer-related medical problems, and end-of-life issues.

Patient-Controlled Analgesia Following Lumbar Spinal Fusion Surgery Is Associated With Increased Opioid Consumption and Opioid-Related Adverse Events.

BACKGROUND: Optimal postoperative pain control is critical after spinal fusion surgery. There remains significant variability in the use of postoperative intravenous opioid patient-controlled analgesia (PCA) and few data evaluating its utility compared with nurse-controlled analgesia (NCA) among patients with lumbar fusion. OBJECTIVE: To investigate the efficacy of postoperative PCA compared with NCA to improve opiate prescription practices. METHODS: A retrospective review from a single institution was conducted in consecutive patients treated with posterior lumbar spinal fusion for degenerative pathology. Patients were divided into cohorts on the basis of postoperative treatment with PCA or NCA. Postoperative pain scores, length of stay, and total opioid consumption data were collected. Patients were stratified according to preoperative opioid consumption as opioid naive (0 morphine milligram equivalents [MME] daily), low consumption (1-60 MME), high consumption (61-90 MME), or very high consumption (>90 MME). RESULTS: A total of 240 patients were identified, including 62 in the PCA group and 178 in the NCA group. PCA patients had higher mean preoperative opioid consumption than NCA patients (49.2 vs 24.3 MME, P = .009). PCA patients had higher mean opioid consumption in the first 72 h in all 4 of the preoperative opioid consumption subcategories. Pain control and adverse event rates were similar between PCA and NCA in the low to high preoperative opioid consumption groups. CONCLUSION: Postoperative PCA is associated with significantly more opioid consumption in the first 72 h after surgery and equal or worse postoperative pain scores compared with NCA after lumbar spinal fusion surgery.

Microvascular Decompression of the Trigeminal Nerve with Petrous Sling Technique: Surgical Video.

The retrosigmoid approach for microvascular decompression of the trigeminal nerve (TN) is an established and highly effective technique for the treatment of trigeminal neuralgia due to vascular compression. It is common to place a pledget or other cushion material between the source of vascular compression, typically the superior cerebellar artery (SCA), and the TN after vessel mobilization and decompression. A previous study demonstrated the use of a tentorial sling on the SCA to maintain decompression of the TN, with encouraging results.1 In this video, we demonstrate a novel technique using a Gore-Tex (W. L. Gore & Associates, Newark, Delaware) sling wrapped around the SCA and secured with a vascular clip on the petrous dura to maintain decompression of the TN (Video 1). Informed consent was obtained from the patient. He tolerated the procedure well with excellent pain relief and was discharged on postoperative day 1.

Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus.

In leptin-deficient ob/ob mice, obesity and diabetes are associated with abnormal development of neurocircuits in the hypothalamic arcuate nucleus (ARC)1, a critical brain area for energy and glucose homeostasis2,3. As this developmental defect can be remedied by systemic leptin administration, but only if given before postnatal day 28, a critical period (CP) for leptin-dependent development of ARC neurocircuits has been proposed4. In other brain areas, CP closure coincides with the appearance of perineuronal nets (PNNs), extracellular matrix specializations that restrict the plasticity of neurons that they enmesh5. Here we report that in humans as well as rodents, subsets of neurons in the mediobasal aspect of the ARC are enmeshed by PNN-like structures. In mice, these neurons are densely-packed into a continuous ring that encircles the junction of the ARC and median eminence, which facilitates exposure of ARC neurons to the circulation. Most of the enmeshed neurons are both GABAergic and leptin receptor-positive, including a majority of Agrp neurons. Postnatal formation of the PNN-like structures coincides precisely with closure of the CP for Agrp neuron maturation and is dependent on input from circulating leptin, as postnatal ob/ob mice have reduced ARC PNN-like material that is restored by leptin administration during the CP. We conclude that neurons crucial to metabolic homeostasis are enmeshed by PNN-like structures and organized into a densely packed cluster situated circumferentially at the ARC-ME junction, where metabolically-relevant humoral signals are sensed.

Accuracy in Deep Brain Stimulation Electrode Placement: A Single-Surgeon Retrospective Analysis of Sterotactic Error in Overlapping and Non-Overlapping Surgical Cases.

BACKGROUND: Many surgeons utilize assistants to perform procedures in more than one operating room at a given time using a practice known as overlapping surgery. Debate has continued as to whether overlapping surgery improves the efficiency and access to care or risks patient safety and outcomes. OBJECTIVE: To examine effects of overlapping surgery in deep brain stimulation (DBS) for movement disorders. METHODS: In this retrospective analysis of overlapping and non-overlapping cases, we evaluated stereotactic accuracy, operative duration, length of hospital stay, and the presence of hemorrhage, wound-related complications, and hardware-related complications requiring revision in adults with movement disorders undergoing DBS. RESULTS: Of 324 cases, 141 (43.5%) were overlapping and 183 (56.5%) non-overlapping. Stereotactic error, number of brain penetrations, and postoperative length of hospitalization did not differ significantly (p ≥ 0.08) between the overlapping and non-overlapping groups. Mean operative duration was significantly longer for overlapping (81/141 [57.4%], 189.5 ± 10.8 min) than for non-overlapping cases (79/183 [43.2%], 169.9 ± 7.6 min; p = 0.004). There were no differences in rates of wound-related complications or hemorrhages, but overlapping cases had a significantly higher rate of hardware-related complications requiring revision (7/141 [5.0%] vs. 0/183 [0%]; p = 0.002). CONCLUSIONS: Overlapping and non-overlapping cases had comparable DBS lead placement accuracy. Overlapping cases had a longer operative duration and had a higher rate of hardware-related complications requiring revision.

Revisiting How the Brain Senses Glucose-And Why.

Glucose-sensitive neurons have long been implicated in glucose homeostasis, but how glucose-sensing information is used by the brain in this process remains uncertain. Here, we propose a model in which (1) information relevant to the circulating glucose level is essential to the proper function of this regulatory system, (2) this input is provided by neurons located outside the blood-brain barrier (BBB) (since neurons situated behind the BBB are exposed to glucose in brain interstitial fluid, rather than that in the circulation), and (3) while the efferent limb of this system is comprised of neurons situated behind the BBB, many of these neurons are also glucose sensitive. Precedent for such an organizational scheme is found in the thermoregulatory system, which we draw upon in this framework for understanding the role played by brain glucose sensing in glucose homeostasis.

Procedural Variables Influencing Stereotactic Accuracy and Efficiency in Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation (DBS) is well-established, evidence-based therapy for Parkinson disease, essential tremor, and primary dystonia. Clinical outcome studies have recently shown that "asleep" DBS lead placement, performed using intraoperative imaging with stereotactic accuracy as the surgical endpoint, has motor outcomes comparable to traditional "awake" DBS using microelectrode recording (MER), but with shorter case times and improved speech fluency. OBJECTIVE: To identify procedural variables in DBS surgery associated with improved surgical efficiency and stereotactic accuracy. METHODS: Retrospective review of 323 cases with 546 leads placed (August 2011-October 2014). In 52% (n = 168) of cases, patients were asleep under general anesthesia without MER. Multivariate regression identified independent predictors of reduced surgery time and improved stereotactic accuracy. RESULTS: MER was an independent contributor to increased procedure time (+44 min; P = .03). Stereotactic accuracy was better in asleep patients. Accuracy was improved with frame-based stereotaxy at head of bed 0° vs frameless stereotaxy at head of bed 30°. Improved accuracy was also associated with shorter procedures (r = 0.17; P = .049). Vector errors were evenly distributed around the planned target for the globus pallidus internus, but directionally skewed for the subthalamic (medial-posterior) and ventral intermediate nuclei (medial-anterior). CONCLUSION: Distinct procedural variables in DBS surgery are associated with reduced case times and improved stereotactic accuracy.

Deep brain stimulation for intractable neuropathic facial pain.

OBJECTIVE Deep brain stimulation (DBS) is a well-established, evidence-based therapy with FDA approval for Parkinson's disease and essential tremor. Despite the early successful use of DBS to target the sensory thalamus for intractable facial pain, subsequent studies pursuing various chronic pain syndromes reported variable efficacy, keeping DBS for pain as an investigational and "off-label" use. The authors report promising results for a contemporary series of patients with intractable facial pain who were treated with DBS. METHODS Pain outcomes for 7 consecutive patients with unilateral, intractable facial pain undergoing DBS of the ventral posteromedial nucleus of the thalamus (VPM) and the periaqueductal gray (PAG) were retrospectively reviewed. Pain was assessed preoperatively and at multiple postoperative time points using the visual analog scale (VAS), the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), and the Pain Disability Index (PDI). RESULTS VAS scores significantly decreased from a mean ± SD of 9.0 ± 1.3 preoperatively to 2.6 ± 1.5 at 1 year postoperatively (p = 0.001). PDI scores decreased from a mean total of 48.5 to 28.5 (p = 0.01). SF-MPQ-2 scores decreased from a mean of 4.6 to 2.4 (p = 0.03). Notably, several patients did not experience maximum improvement until 6-9 months postoperatively, correlating with repeated programming adjustments. CONCLUSIONS DBS of the VPM and PAG is a potential therapeutic option for patients suffering from severe, intractable facial pain refractory to other interventions. Improved efficacy may be observed over time with close follow-up and active DBS programming adjustments.