Quantitative analysis of external carotid artery bypass donor vessels by recipient and approach.

INTRODUCTION: Utilization an in-situ pedicle of the external carotid artery (ECA) as an arterial donor can allow for the successful augmentation or replacement of flow to a large vascular territory. We propose a mathematical model for quantitatively analyzing and grading the suitability of donor and recipient bypass vessels based on a set of anatomical and surgical variables in order to predict which pair has the greatest possibility for success. Using this method, we analyze all of the potential donor-recipient pairs for each ECA donor vessel-including the superficial temporal (STA), middle meningeal (MMA), and occipital (OA) arteries. METHODS: The ECA pedicles were dissected in frontotemporal, middle fossa, subtemporal, retrosigmoid, far lateral, suboccipital, supracerebellar, and occipital transtentorial approaches. For each approach, every potential donor-recipient pair was identified, and donor length and diameter were measured as well as depth of field, angle of exposure, ease of proximal control, maneuverability, and length and diameter of the recipient segment. Anastomotic pair scores were determined by adding the weighted donor and recipient. RESULTS: The best overall anastomotic pairs were OA-vertebral artery (V3, 17.1) and STA-insular (M2, 16.3) and STA-sylvian (M3, 15.9) segments of the middle cerebral artery. Other strong anastomotic combinations were OA- telovelotonsillar (15) and OA- tonsilomedullary (14.9) segments of the posterior inferior cerebellar artery, and MMA-lateral pontomesencephalic segment of the superior cerebellar artery (14.2). CONCLUSIONS: This novel model for anastamotic pair scoring can serve as a useful clinical tool for selecting the optimal donor, recipient, and approach combination that can help facilitate a successful bypass.

Variation in Cervical Pedicle Morphology: Important Considerations for Posterior Cervical Procedures.

BACKGROUND: Safe posterior cervical spine surgery requires in-depth understanding of the surgical anatomy and common variations. The cervical pedicle attachment site to the vertebral body (VB) affects the location of exiting nerve roots and warrants preoperative evaluation. The relative site of attachment of the cervical pedicle has not been previously described. OBJECTIVE: To describe the site of the pedicle attachment to the VB in the subaxial cervical spine. METHODS: Cervical spine computed tomography scans without any structural, degenerative, or traumatic pathology as read by a board-certified neuroradiologist during 2021 were reviewed. Multiplanar reconstructions were created and cross-registered. The pedicle's attachment to the VB was measured relative to the VB height using a novel calculation system. RESULTS: Fifty computed tomography scans met inclusion criteria yielding 600 total pedicles between C3-T1 (100 per level). The average patient age was 26 ± 5.3 years, and 21/50 (42%) were female. 468/600 (78%) pedicles attached in the cranial third of the VB, 132/600 (22%) attached in the middle third, and 0 attached to the caudal third. The highest prevalence of variant anatomy occurred at C3 (36/100 C3 pedicles; 36%). CONCLUSION: In the subaxial cervical spine, pedicles frequently attach to the top third of the VB, but significant variation is observed. The rate of variation is highest at C3 and decreases linearly with caudal progression down the subaxial cervical spine to T1. This is the first report investigating this morphological phenomenon.

Tailored Surgical Access to the Cavernous Sinus and Parasellar Region: Assessment of Cavernous Sinus Entry Corridors and the Periclinoid and Pericavernous Surgical Maneuvers.

BACKGROUND: Lesions involving the cavernous sinus (CS) represent some of the most challenging pathologies of the skull base owing to the dense traversing and surrounding neurovasculature. Extradural exposure and preparation of this region, whether as initial preparation for a combined intra-extradural approach or as the main avenue of surgical exposure, can enlarge surgical corridors and minimize the need for brain retraction in this very confined space. We provide a detailed assessment of the entry corridors to the CS that are available within each approach, the surgical exposure and freedom provided by each of these corridors, and demonstrate how extradural and intradural preparation of these corridors can be used to widen the available working space and facilitate surgery. METHODS: Pterional, frontotemporal-orbital, frontotemporal-orbitozygomatic, frontotemporal-zygomatic, perilabyrinthine transtentorial, and endoscopic transnasal transsphenoidal approaches were performed on cadaveric heads to access the perisellar and CS regions. Periclinoid maneuvers (extradural cutting of the meningo-orbital band, anterior clinoidectomy, unroofing of the optic canal, opening of the superior orbital fissure, displacement of the extra-annular structures, opening of the annulus of Zinn, and interdural dissection), pericavernous maneuvers (intradural cutting of the distal dural ring, mobilization of the supraclinoid internal carotid artery, opening of the oculomotor porus, and mobilization of cranial nerve (CN) III), peritrigeminal extensions (extradural mobilization of CN V2 [maxillary] and/or V3 [mandibular]), and other surgical maneuvers were performed and evaluated. The CS was divided into 8 anatomical compartments and 9 entry corridors were described, and exposure and freedom were assessed accordingly. RESULTS: Intradurally, the standard unextended pterional, frontotemporal-orbital, and frontotemporal orbitozygomatic transsylvian approaches provided access solely to the parasellar entry corridor into the superior wall of the CS. Expanding these approaches with extradural periclinoid maneuvers allowed for subsequent application of the intradural pericavernous maneuvers and enlargement of the parasellar corridor and exposure of the carotid cave. Extradurally, the frontotemporal-orbital approach could be expanded via application of periclinoid maneuvers, which provided access to the anterior portions of the main lateral wall entry corridors. The frontotemporal-orbitozygomatic approach could also be expanded with periclinoid maneuvers to provide extradural access to all 6 lateral wall entry corridors. The extradural frontotemporal-zygomatic approach only provided exposure following interdural dissection, which allowed for access to the inferolateral entry corridors into the lateral wall. Extradural peritrigeminal extension in the frontotemporal-orbitozygomatic and frontotemporal-zygomatic approaches allows for enlargement of the supramaxillary and pre- and postmandibular corridors. The perilabyrinthine approach to the posterior wall was enlarged with opening of Dorello's canal and the endoscopic transnasal transsphenoidal approach was enlarged with opening of the optic canal. CONCLUSIONS: Targeted extradural preparation optimizes exposure and significantly improves access to deep-seated targets by enhancing surgical maneuverability through the unlocking of neurovascular structures and widening of surgical corridors without the need for additional brain retraction.

A novel 3D surgical neuroanatomy course for medical students: Outcomes from a pilot 6-week elective.

BACKGROUND: Developing and maintaining a three-dimensional working knowledge of neuroanatomy is an essential skill in neurosurgery. However, conventional 2D head, neck, and neuroanatomy education is typically characterized by the separate rote learning of constituent tissues and often fails to provide learners with a contextual understanding of the relationships between these highly complex and interconnected structures. This can pose a significant challenge to medical students entering neurosurgery who lack a topographic understanding of intracranial anatomy. METHODS: We report on the design and efficacy of a novel 6-part 3D surgical neuroanatomy pilot elective for medical students that utilized a navigation-based pedagogical technique with the goal of providing students with a framework for developing a 3D mental map of the skull base, neurovasculature, ventricular system, and associated brain regions. Students took on the perspective of physically traveling along the paths of key structures with a 360-degree view of surrounding anatomy such that they could appreciate the integration and relative spatial relationships of the varying tissues within the cranium. Mental navigation exercises and pre- and post-course surveys were used to assess students' baseline and learned familiarity with the different anatomical regions covered. RESULTS: At the conclusion of the course, all students were able to successfully complete all of the multifaceted mental navigation exercises. Post-course survey data indicated that respondents perceived significant increases in their knowledge of cranial nerves; anterior, middle, and posterior skull base anatomy; anterior and posterior cranial circulation; and the ventricular system. CONCLUSION: 3D navigation-based fly-through instruction is a novel and effective technique for teaching complex anatomy and can provide learners with the foundational skills for developing and maintaining a 3D mental map of intracranial anatomy.

Clinical Significance of Redundant Nerve Roots in Patients with Lumbar Stenosis Undergoing Minimally Invasive Tubular Decompression.

OBJECTIVE: Symptomatic lumbar spinal stenosis (LSS) is a common indication for surgery in the elderly. Preoperative radiographic evaluation of patients with LSS often reveals redundant nerve roots (RNRs). The clinical significance of RNRs is uncertain. RNRs have not been studied in the setting of minimally invasive surgery. This study investigates the relationship between RNRs and clinical outcomes after minimally invasive tubular decompression. METHODS: Chart review was performed for patients with degenerative LSS who underwent minimally invasive decompression. Preoperative magnetic resonance imaging parameters were assessed, and patient-reported outcomes were analyzed. RESULTS: Fifty-four patients underwent surgery performed at an average of 1.8 ± 0.8 spinal levels. Thirty-one patients (57%) had RNRs. Patients with RNRs were older (median = 72 years vs. 66 years, P = 0.050), had longer median symptom duration (32 months vs. 15 months, P < 0.01), and had more levels operated on (2.1 vs. 1.4; P < 0.01). The median follow-up after surgery was 2 months (range = 1.3-12 months). Preoperative and postoperative patient-reported outcomes were similar based on RNR presence. Patients without RNRs had larger lumbar cross-sectional areas (CSAs) (median = 121 mm2 vs. 95 mm2, P = 0.014) and the index-level CSA (52 mm2 vs. 34 mm2, P = 0.007). The CSA was not correlated with RNR morphology or location. CONCLUSIONS: Preoperative RNRs are associated with increased age, symptom duration, and lumbar stenosis severity. Patients improved after minimally invasive decompression regardless of RNR presence. RNR presence had no effect on short-term clinical outcomes. Further study is required to assess their long-term significance.

A Novel Endoscopic Technique for Biopsy and Tissue Diagnosis for a Paraspinal Thoracic Tumor in a Pediatric Patient: A Case Report.

BACKGROUND: Conventional approaches to the thoracic spine can require extensive tissue dissection, bony disruption, and instability that may warrant the need for instrumentation and fusion. Furthermore, anterior approaches may require the involvement of various surgeons from multiple disciplines to ensure a successful operation and mitigate complications. Currently, available minimally invasive approaches still require bony removal and usually rely heavily on computed tomography (CT)-guided imaging without direct gross visualization. Endoscopic spinal procedures have provided an ultra-minimally invasive alternative to access many areas in and around the spinal column. METHODS: We present a 12-year-old boy with a right-sided 2.0 × 3.2-cm paravertebral lesion at the level of T5. The patient successfully underwent an endoscopic approach to the lesion with minimal tissue and bony disruption for tissue diagnosis and tumor resection. RESULTS: At initial and 6-month follow-up, the patient remained asymptomatic and without issues. CONCLUSIONS: We demonstrate here the feasibility and suggest the safety of a posterior ultra-minimally invasive endoscopic spinal approach to obtain a tissue biopsy of an incidentally found ventrolateral paraspinal tumor in the thoracic region in a pediatric patient. This minimal approach can prove to achieve similar results as other approaches that may otherwise necessitate more extensive or transthoracic procedures.

Combination of volume-rendering 3D surface modeling and medical illustration to capture the living fetus.

OBJECTIVE: A good medical illustration renders essential aspects of a procedure or condition faithfully, yet idealizes it enough to make it widely applicable. Unfortunately, the live fetus is generally hidden from sight, and illustrating it relies either on autopsy material or manipulated newborn images. High-definition volume rendering of diagnostic imaging data can represent hidden conditions with an almost lifelike realism but is limited by the resolution and artifacts of the data capture. We have combined both approaches to enhance the accuracy and didactic value of illustrations of fetal conditions. METHODS: Three examples, of increasing complexity, are presented to demonstrate the creation of medical illustrations of the fetus based on semiautomatic computerized posthoc manipulation of diagnostic images. RESULTS: The end product utilizes the diagnostic accuracy of ultrasound and magnetic resonance imaging of the fetuses and the spatial manipulation of 3D models to create a lifelike, accurate and informative image of the fetal anomalies. CONCLUSION: Volume-rendering and 3D surface modeling can be combined with medical illustration to create realistic and informative images of the developing fetus, using a level of detail that is tailored to the intended audience.

Transforaminal Endoscopic Approach for Large-Sample Tumor Biopsy using Beveled Working Channel for Core Technique: A Technical Note.

BACKGROUND: Identifying the histopathological diagnosis of a spinal tumor is the necessary step prior to pursuing subsequent treatment. Both minimally invasive and open spinal procedures have been described as useful methods of obtaining tumor tissue for diagnosis but differ by their limitations. Minimally invasive techniques, such as computed tomography-guided biopsies, can expose the patient to radiation, and the tissue obtained may be nondiagnostic. Tubular and open procedures require collateral soft-tissue damage and may require bony removal leading to iatrogenic injury. Endoscopic approaches to the spine can be employed to avoid treatment delay in diagnosis, decrease length of stay, and provide adequate tissue for diagnosis. METHODS: We describe the surgical planning, tumor localization, and transforaminal endoscopic approach for tissue diagnosis of a lumbar spinal mass in a patient with a known history of Hodgkin lymphoma and non-Hodgkin lymphoma after a nondiagnostic computed tomography- guided biopsy. Final histopathological diagnosis of the lumbar spinal mass was consistent with large B-cell non-Hodgkin lymphoma. CONCLUSIONS: We demonstrate the application of an endoscopic transforaminal approach in spine oncology. We also describe our technique on how we use a beveled working channel to obtain a large tissue core sample for definitive diagnosis.

Poly-4-Hydroxybutyric Acid Mesh Compares Favorably With Acellular Dermal Matrix in Tissue Expander-Based Breast Reconstruction.

BACKGROUND: Acellular dermal matrix (ADM) is commonly used during immediate expander-based breast reconstruction, with potential advantages of greater intraoperative expansion, decreased time to complete expansion, and decreased rates of capsular contracture. However, ADM is associated with increased infection rate, seroma, and subsequent reconstructive failure. Poly-4-hydroxybutyric acid (P4HB) mesh is a large pore, biosynthetic scaffold shown to fully resorb and incorporate host tissues within 18 months. We sought to compare outcomes between the use of P4HB and ADM in immediate retropectoral expander-based reconstruction. METHODS: One hundred ninety-two consecutive cases (107 patients) of breast reconstruction using ADM were compared with a subsequent cohort of 112 cases (62 patients) using P4HB mesh. In all patients, reconstruction was performed immediately after mastectomy by a single surgeon, and outcomes were compared between groups. RESULTS: Baseline characteristics were similar between the P4HB and ADM groups. Overall infection rates were lower, but not significantly with P4HB (11% vs 17%, P = 0.18). Time to drain removal was significantly lower with P4HB (15 vs 18 days, P = 0.008), although there was no difference in rates of seroma (0.9% vs 3%, P = 0.43). Similar numbers of patients underwent external beam radiation (22% vs 24%) and received chemotherapy in each group (48% vs 45%). By univariate analysis, all odds ratios were decreased with use of P4HB, including risk of major complications (0.55), seroma (0.17), infection (0.59), need for reoperation (0.78), and skin necrosis (0.77). CONCLUSIONS: Initial findings suggest P4HB mesh to be a safe alternative to ADM in expander-based breast reconstruction, with trends toward decreased rates of infection, seroma, and need for device removal using P4HB mesh. Although our results are limited to a small series of initial patients, P4HB mesh may be a promising novel technique to decrease complications inherent to use of ADM at a reduced material cost.

Medical Students' Perceived Interests and Concerns for a Career in Neurosurgery.

OBJECTIVE: The factors that attract and concern medical students about a career in neurosurgery have never been clearly characterized or delineated in a large nationwide cohort of medical students intending to pursue a career in neurosurgery. The objective of the present study was to characterize the factors that influence medical student interest in neurosurgery and assess the effects of a formal neurosurgery training course on participants' perceptions of a career in neurosurgery. METHODS: Before the Medical Student Neurosurgery Training Camp for subinternship preparation, registered students were surveyed about their interest level in neurosurgery, factors that attracted or concerned them about a career in neurosurgery, attendance at a national neurosurgery conference or course, formal clinical neurosurgery exposure in medical school, and whether they had a resident or attending mentor in neurosurgery. At the end of the course, all the participants completed the surveyed again. P < 0.05 was considered significant on Pearson's χ2 and Fisher's exact tests for categorical variables and 2-tailed paired Student's t tests for continuous variables. RESULTS: Of the training camp attendees, >95% completed both pre- and postcourse surveys, including 41 first-year, 19 second-year, 30 third-year, and 5 fourth-year medical school students. The most common factors that concerned students about a career in neurosurgery were work-life balance (76%) and competitiveness (56%). All factors of concern were decreased in the postcourse survey, except for competitiveness. A small cohort (8.4%) of students had no concerns about a career in neurosurgery; this cohort had doubled to 17% after the course (P < 0.05). The students that indicated no concern had a greater postcourse interest level in neurosurgery (95.8 ± 8.7 vs. 86.7 ± 20.5; P < 0.05). Student reasons for an interest in neurosurgery included intellectually stimulating work (94%), interest in neurosciences (93%), effect on patients (84%), innovation and new technology (80%), research opportunities (77%), and prestige (24%). All reasons increased after the course, with the exception of prestige, which decreased to 22%. CONCLUSION: A training camp for students pursuing a neurosurgery subinternship was effective in providing transparency and positively influencing the factors that attract and concern students about a career in neurosurgery. Characterization of medical student perceptions of neurosurgery from a large, nationwide cohort of students pursuing a subinternship has provided novel data and could help identify factors protecting against burnout later in life.

Oncologic benefits of dural resection in spinal meningiomas: a meta-analysis of Simpson grades and recurrence rates.

OBJECTIVE: While resection of the dural attachment has been shown by Simpson and others to reduce recurrence rates for intracranial meningiomas, the oncological benefit of dural resection for spinal meningiomas is less clear. The authors performed a systematic analysis of the literature, comparing recurrence rates for patients undergoing various Simpson grade resections of spinal meningiomas to better understand the role of dural resection on outcomes after resection of spinal meningiomas. METHODS: The PubMed/Medline database was systematically searched to identify studies describing oncological and clinical outcomes after Simpson grade I, II, III, or IV resections of spinal meningiomas. RESULTS: Thirty-two studies describing the outcomes of 896 patients were included in the analysis. Simpson grade I, grade II, and grade III/IV resections were performed in 27.5%, 64.6%, and 7.9% of cases, respectively. The risk of procedure-related complications (OR 4.75, 95% CI 1.27-17.8, p = 0.021) and new, unexpected postoperative neurological deficits (OR ∞, 95% CI NaN-∞, p = 0.009) were both significantly greater for patients undergoing Simpson grade I resections when compared with those undergoing Simpson grade II resections. Tumor recurrence was seen in 2.8%, 4.1%, and 39.4% of patients undergoing Simpson grade I, grade II, and grade III/IV resections over a mean radiographic follow-up period of 99.3 ± 46.4 months, 95.4 ± 57.1 months, and 82.4 ± 49.3 months, respectively. No significant difference was detected between the recurrence rates for Simpson grade I versus Simpson grade II resections (OR 1.43, 95% CI 0.61-3.39, p = 0.43). A meta-analysis of 7 studies directly comparing recurrence rates for Simpson grade I and II resections demonstrated a trend toward a decreased likelihood of recurrence after Simpson grade I resection when compared with Simpson grade II resection, although this trend did not reach statistical significance (OR 0.56, 95% CI 0.23-1.36, p = 0.20). CONCLUSIONS: The results of this analysis suggest with a low level of confidence that the rates of complications and new, unexpected neurological deficits after Simpson grade I resection of spinal meningiomas are greater than those seen with Simpson grade II resections, and that the recurrence rates for Simpson grade I and grade II resections are equivalent, although additional, long-term studies are needed before reliable conclusions may be drawn.

Spinal dural resection for oncological purposes: a systematic analysis of risks and outcomes in patients with malignant spinal tumors.

OBJECTIVE: Oncological outcomes for many malignant primary spinal tumors and isolated spinal metastases have been shown to correlate with extent of resection. For tumors with dural involvement, some authors have described spinal dural resection at the time of tumor resection in the interest of improving oncological outcomes. The complication profile associated with resection of the spinal dura for oncological purposes, however, and the relative influence of resecting tumor-involved dura on progression-free survival are not well defined. The authors performed a systematic review of the literature and identified cases in which the spinal dura was resected for oncological purposes in the interest of better understanding the associated risks and outcomes of this technique. METHODS: Electronic databases (PubMed/MEDLINE, Scopus) were systematically searched to identify studies that reported clinical and/or oncological outcomes of patients with malignant spinal neoplasms undergoing resection of tumor-involved dura at the time of surgical intervention. RESULTS: Ten articles describing 15 patients were included in the analysis. The most common tumor histologies were chordoma (3/15, 20%), giant cell tumor (3/15, 20%), epithelioid sarcoma (2/15, 13.3%), osteosarcoma (2/15, 13.3%), and metastasis (2/15, 13.3%). Procedure-related complications were reported in 40% of patients. A trend was seen toward an increased complication rate in redo (66.7%) versus index (16.7%) operations, but this trend did not reach statistical significance (p = 0.24). New, unexpected postoperative neurological deficits were seen in 3 patients (of 14 reporting, 21.4%). A single patient experienced a profound, unexpected neurological deterioration (paraparesis/paraplegia) after surgery, which reportedly improved considerably at latest follow-up. Tumor recurrence was seen in 3 cases (of 12 reporting, 25%) at a mean of 28.34 ± 21.1 months postoperatively. The overall mean radiographic follow-up period was 49.6 ± 36.5 months. CONCLUSIONS: Resection of the spinal dura for oncological purposes is rarely performed, although a limited number of reports and small series have demonstrated that it is feasible. Spinal dural resection is primarily performed in patients with isolated, primary spinal neoplasms with an intent to cure. The risk associated with spinal dura resection is nontrivial and the complication profile is significant. The influence of dural resection on oncological outcomes is not well defined, and further study is needed before definitive conclusions may be drawn regarding the oncological benefit of dural resection for any particular patient or pathology.

Posterior Nerve-Sparing Multilevel Cervical Corpectomy and Reconstruction for Metastatic Cervical Spine Tumors: Case Report and Literature Review.

BACKGROUND: Cervical spine metastases with circumferential spinal cord compression often are treated with combined anteroposterior decompression and stabilization. In patients with large anterior neck masses, previous radiotherapy to the neck, or previous anterior neck surgery, however, anterior approaches may pose additional risk. In such cases, posterior-only approaches that allow for circumferential decompression and anterior column reconstruction may be beneficial. CASE DESCRIPTION: We present the case of a 70-year-old man with follicular thyroid carcinoma metastatic to the cervical spine causing spinal cord compression. We used a posterior-only approach for a C6-C7 partial corpectomy and posterior decompression and fusion from C2 to T2. Our technique involved preoperative embolization of the right vertebral artery to safely gain access to the ventral surface of the spinal cord and vertebral bodies. Anterior column support was provided by a chest tube/polymethylmethacrylate construct, allowing the implant to be placed within the anterior column from a posterior approach without nerve root sacrifice. The patient tolerated the procedure well. He had no postoperative neurologic deficits. Two months later, he underwent a total thyroidectomy followed by stereotactic radiotherapy to the tumor bed (2700 cGy total, 3 fractions). At 1-year follow-up, he was active and without significant pain or focal neurologic deficits. CONCLUSIONS: We propose a novel approach to ventral/circumferential cervical spine tumors that combines epidural decompression and cervical stabilization via a posterior-only approach. By using a chest tube/polymethylmethacrylate construct, anterior column support can be achieved through a posterior approach without nerve root sacrifice.

Sub-paresthesia spinal cord stimulation reverses thermal hyperalgesia and modulates low frequency EEG in a rat model of neuropathic pain.

Paresthesia, a common feature of epidural spinal cord stimulation (SCS) for pain management, presents a challenge to the double-blind study design. Although sub-paresthesia SCS has been shown to be effective in alleviating pain, empirical criteria for sub-paresthesia SCS have not been established and its basic mechanisms of action at supraspinal levels are unknown. We tested our hypothesis that sub-paresthesia SCS attenuates behavioral signs of neuropathic pain in a rat model, and modulates pain-related theta (4-8 Hz) power of the electroencephalogram (EEG), a previously validated correlate of spontaneous pain in rodent models. Results show that sub-paresthesia SCS attenuates thermal hyperalgesia and power amplitude in the 3-4 Hz range, consistent with clinical data showing significant yet modest analgesic effects of sub-paresthesia SCS in humans. Therefore, we present evidence for anti-nociceptive effects of sub-paresthesia SCS in a rat model of neuropathic pain and further validate EEG theta power as a reliable 'biosignature' of spontaneous pain.

Thalamic Bursts Down-regulate Cortical Theta and Nociceptive Behavior.

We tested the relation between pain behavior, theta (4-8 Hz) oscillations in somatosensory cortex and burst firing in thalamic neurons in vivo. Optically-induced thalamic bursts attenuated cortical theta and mechanical allodynia. It is proposed that thalamic bursts are an adaptive response to pain that de-synchronizes cortical theta and decreases sensory salience.

Peripheral Mechanisms of Itch.

A multitude of exogenous environmental stimuli and endogenous molecular and cellular components interface directly or indirectly with the free nerve endings of sensory nerves in the skin. Environmental stimuli include substances derived from the microbiome and materials, such as allergens, that otherwise come in contact with the skin. Endogenous stimuli include components of or mediators derived from the epidermal barrier, keratinocytes, mast cells, and additional resident and skin-homing immune cells. The sensation of itch is ultimately provoked by mediators that interact with and activate pruriceptors on the sensory nerve fibers. These peripheral fibers convey signals from the skin to the dorsal root and trigeminal ganglia and on to the spinal cord and brain where central processing of the itch sensation occurs. A discussion of the nature and sources of itch stimuli and receptors in the periphery form the basis of this chapter. The development of drugs that target these processes is in the process of revolutionizing therapeutic approaches to itch.