Selective denervation of the corrugator supercilii muscle for the treatment of idiopatic trigeminal neuralgia purely paroxysmal distributed in the supraorbital and suprathrochlear dermatomes.

INTRODUCTION: Idiopatic trigeminal neuralgia purely paroxysmal (ITNp) distributed in the supraorbital and suprathrochlear dermatomes (SSd), refractory to conventional treatments have been linked to the hyperactivity of the corrugator supercilii muscle (CSM). In these patients, the inactivation of the CSM via botulinum toxin type A (BTA) injections has been proven to be safe and effective in reducing migraine burden. The main limitation of BTA is the need of repetitive injections and relative high costs. Based on the study of the motor innervation of the CSM, we describe here an alternative approach to improve these type of migraines, based on a minimally invasive denervation of the CSM. MATERIALS AND METHODS: Motor innervation and feasibility of selective CSM denervation was first studied on fresh frozen cadavers. Once the technique was safely established, 15 patients were enrolled. To be considered eligible, patients had to meet the following criteria: positive response to BTA treatment, migraine disability assessment score > 24, > 15 migraine days/month, no occipital/temporal trigger points and plausible reasons to discontinue BTA treatment. Pre- and post- operative migraine headache index (MHI) were compared, and complications were classified following the Clavien-Dindo classification (CDC). RESULTS: Fifteen patients (9 females and 6 males) underwent the described surgical procedure. The mean age was 41 ± 10 years. Migraine headache episodes decreased from 24 ± 4 day/month to 2 ± 2 (p < 0.001) The MHI decreased from 208 ± 35 to 10 ± 11 (p < 0.001). One patient (7%) had a grade I complication according to the CDC. No patient needed a second operative procedure. CONCLUSIONS: Our findings suggest that the selective CSM denervation represents a safe and minimally invasive approach to improve ITNp distributed in the SSd associated with CSM hyperactivation. TRIAL REGISTRATION: The data collection was conducted as a retrospective quality assessment study and all procedures were performed in accordance with the ethical standards of the national research committee and the 1964 Helsinki Declaration and its later amendments.

Sensate immediate breast reconstruction.

As breast cancer therapies and associated oncologic outcomes continue to improve, greater attention has been placed on quality-of-life issues after breast cancer and breast cancer risk-reducing treatments. The loss of sensation that typically occurs after mastectomy can have significant negative psychological, sexual, and functional impact on patients after surgery. Further, injury of nerves not only leads to numbness, but can also cause chronic neuropathic pain, which can be very debilitating to affected patients. In order to minimize these impacts, there is expanding uptake of surgical approaches that preserve nerves at the time of mastectomy and reconstruct injured nerves either during mastectomy or during delayed reconstruction. These advances have been facilitated by anatomic studies investigating different variants of intercostal anatomy and better understanding the course of the nerves innervating the mastectomy skin and nipple-areolar complex (NAC). With improved knowledge of the intercostal nerve anatomy, surgeons are able to carefully preserve nerves at the time of mastectomy, thus improving sensory outcomes. Additionally, nerve reconstruction techniques have advanced, particularly with newer nerve allograft technologies, which allows for nerve reconstruction to be done both at the time of mastectomy, as well as in a delayed fashion. The focus of this article is to describe the current state of sensory preservation and immediate reinnervation at the time of mastectomy and the advances that have allowed for these new approaches.

Active Occipital Motion with Digipressure as Preoperative Screening in Migraine Surgery.

Background: Modern surgical therapy of chronic headaches/migraines is essentially based on the release/neurolysis of extracranial nerves, which, when compressed or inflamed, act as trigger points and, as such, trigger headache attacks. The aim of this article was to describe a novel maneuver we use as an aid in the preoperative planning of occipital trigger sites. Methods: In the period of January 2021-September 2023, we operated on 32 patients (11 men, 21 women, age range: 26-68 years), who underwent migraine surgery for occipital trigger point release. All patients were evaluated using the described preoperative maneuver. In a dedicated card, the levels of tenderness at each point were marked accordingly, differentiating them by intensity as nothing (-), mild (+), medium (++), or high (+++). Patients were then operated on at the points corresponding only to the ++ and +++ signs. Results: At 6-month follow-up, we observed significant improvement (>50%) in 29 patients (91%), with complete recovery in 25 patients (78%). Conclusions: In our experience, the maneuver described, in addition to being very simple, has been shown to have good sensitivity and reproducibility. We therefore recommend its use, especially for those surgeons beginning their practice in this particular area of plastic surgery.

Treatment of a patient with small fiber pathology using nerve biopsy and grafting: a case report.

Small fiber pathology is a common clinical entity with a variable clinical presentation and etiology. Unfortunately, little has been described regarding its treatment because a majority of cases are idiopathic. Hence, treatment often consists of symptomatic management of pain and autonomic dysfunction. This report describes a patient who was presented with an undiagnosed pain syndrome thought to be affecting nerves within both lower extremities and causing significant pain. A sural nerve biopsy was performed for diagnostic purposes and nerve repair was performed using Avance nerve allograft (AxoGen Inc., Alachua, FL). Light microscopic evaluation was unremarkable, but electron microscopy revealed small fiber pathology. Postoperatively, the patient experienced a complete resolution of her pain on the involved extremity. These results suggest a potential, novel approach for treatment of such cases and possible mechanisms for the patient's clinical improvement are explored.

Sensory Outcomes after Neurotization in Nipple-sparing Mastectomy and Implant-based Breast Reconstruction.

Background: Mastectomy and breast reconstruction techniques continue to evolve to optimize aesthetic and reconstructive outcomes. However, the loss of sensation after mastectomy remains a major limitation. This article describes our evolution of a novel approach that we first described in 2019, combining recent advances in breast oncologic, reconstructive, and peripheral nerve surgery to optimize sensory outcomes. Methods: Nipple-sparing mastectomy was performed in all patients and involved preservation of lateral intercostal nerves when anatomy was favorable. When nerves could not be preserved without compromising oncologic safety, nipple-areolar complex neurotization was performed using allograft or intercostal autograft from a transected T3, T4, or T5, lateral intercostal nerve to identified subareolar nerve targets. Immediate, prepectoral, direct-to-implant reconstruction was then performed. Acroval one-point moving and one-point static pressure thresholds established baseline sensibility values, which were then repeated at multiple time points postoperatively. Results: Outcomes from 47 women (79 breasts) were assessed prospectively. Mean follow-up was 9.2 months (range 6-14 months). At 6 months postoperatively, over 80% of patients had good-to-excellent one-point moving as well as one-point static sensibility scores averaged across all areas tested. None of the patients developed persistent dysesthesia or clinical evidence of neuroma. Conclusions: This study represents the largest series reported to date of sensibility outcomes after nipple-sparing mastectomy and implant reconstruction with concurrent neurotization. Sensibility results show that this approach allows for preservation of high degrees of breast and nipple-areolar complex sensation in most patients.

Anatomic Anomalies of the Nerves Treated during Headache Surgery.

Background: Headache surgery is a well-established, viable option for patients with chronic head pain/migraines refractory to conventional treatment modalities. These operations involve any number of seven primary nerves. In the occipital region, the surgical targets are the greater, lesser, and third occipital nerves. In the temporal region, they are the auriculotemporal and zygomaticotemporal nerves. In the forehead, the supraorbital and supratrochlear are targeted. The typical anatomic courses of these nerves are well established and documented in clinical and cadaveric studies. However, variations of this "typical" anatomy are quite common and relatively poorly understood. Headache surgeons should be aware of these common anomalies, as they may alter treatment in several meaningful ways. Methods: In this article, we describe the experience of five established headache surgeons encompassing over 4000 cases with respect to the most common anomalies of the nerves typically addressed during headache surgery. Descriptions of anomalous nerve courses and suggestions for management are offered. Results: Anomalies of all seven nerves addressed during headache operations occur with a frequency ranging from 2% to 50%, depending on anomaly type and nerve location. Variations of the temporal and occipital nerves are most common, whereas anomalies of the frontal nerves are relatively less common. Management includes broader dissection and/or transection of accessory injured nerves combined with strategies to reduce neuroma formation such as targeted reinnervation or regenerative peripheral nerve interfaces. Conclusions: Understanding these myriad nerve anomalies is essential to any headache surgeon. Implications are relevant to preoperative planning, intraoperative dissection, and postoperative management.

In-Depth Look at the Anatomical Relationship of the Lesser Occipital Nerve, Great Auricular Nerve, and Spinal Accessory Nerve and Their Implication in Safety of Operations in the Posterior Triangle of the Neck.

BACKGROUND: Migraine surgery is an increasingly popular treatment option for migraine patients. The lesser occipital nerve is a common trigger point for headache abnormalities, but there is a paucity of research regarding the lesser occipital nerve and its intimate association with the spinal accessory nerve. METHODS: Six cadaver necks were dissected. The lesser occipital, great auricular, and spinal accessory nerves were identified and systematically measured and recorded. These landmarks included the longitudinal axis (vertical line drawn in the posterior), the horizontal axis (defined as a line between the most anterosuperior points of the external auditory canals) and the earlobe. Mean distances and standard deviations were calculated to delineate the relationship between the spinal accessory, lesser occipital, and great auricular nerves. RESULTS: The point of emergence of the spinal accessory nerve was determined to be 7.17 ± 1.15 cm lateral to the y axis and 7.77 ± 1.10 caudal to the x axis. The lesser occipital nerve emerges 7.5 ± 1.31 cm lateral to the y axis and 8.47 ± 1.11 cm caudal to the x axis. The great auricular nerve emerges 8.33 ± 1.31 cm lateral to the y axis and 9.4 ±1.07 cm caudal to the x axis. The decussation of the spinal accessory and the lesser occipital nerves was found to be 7.70 ± 1.16 cm caudal to the x axis and 7.17 ± 1.15 lateral to the y axis. CONCLUSION: Understanding the close relationship between the lesser occipital nerve and spinal accessory nerve in the posterior, lateral neck area is crucial for a safer approach to occipital migraine headaches, occipital neuralgia, and new daily persistent headaches and other reconstructive or cosmetic operations.

Nerve Preservation and Allografting for Sensory Innervation Following Immediate Implant Breast Reconstruction.

While newer breast reconstruction approaches utilizing nipple-sparing mastectomy (NSM) techniques and immediate reconstruction can provide excellent aesthetic outcomes, absent postoperative sensation remains a major limitation. Here, we present a novel technique for implant reconstruction combining the latest advances in breast oncologic, reconstructive, and peripheral nerve surgery to improve sensory outcomes. Sixteen women (31 breasts) underwent NSM and prepectoral, direct-to-implant reconstruction. During NSM, careful dissection was performed along the lateral aspect of the breast to preserve any visible intercostal nerves. When nerves could be preserved without compromising oncologic safety, they were left intact within the subcutaneous tissue of the lateral mastectomy skin flap. Nipple/areolar complex (NAC) neurotization was also performed utilizing allograft coapted from transected T4 or T5 lateral intercostal nerves to subareolar nerves identified at the completion of the mastectomy. Of the 12 women (23 breasts) with at least 3 months' follow-up, NAC 2-point discrimination was preserved in 20 breasts (87%), was worse in 2 breasts (9%), and had actually improved in 1 breast (4%). All patients had intact sensation to light touch throughout the majority of, if not their entire, reconstructed breasts. None of the women developed dysesthesias or neuromas. Nerve grafting in conjunction with careful nerve preservation at the time of NSM and implant-based breast reconstruction is safe and effective with a 90% rate of preserved sensation. With longer follow-up, continued return of sensation or possibly improved sensation from baseline can be reasonably anticipated.

The Greater Occipital Nerve and Obliquus Capitis Inferior Muscle: Anatomical Interactions and Implications for Occipital Pain Syndromes.

BACKGROUND: The compression/injury of the greater occipital nerve has been identified as a trigger of occipital headaches. Several compression points have been described, but the morphology of the myofascial unit between the greater occipital nerve and the obliquus capitis inferior muscle has not been studied yet. METHODS: Twenty fresh cadaveric heads were dissected, and the greater occipital nerve was tracked from its emergence to its passage around the obliquus capitis inferior. The intersection point between the greater occipital nerve and the obliquus capitis inferior, and the length and thickness of the obliquus capitis inferior, were measured. In addition, the nature of the interaction and whether the nerve passed through the muscle were also noted. RESULTS: All nerves passed either around the muscle loosely (type I), incorporated in the dense superficial muscle fascia (type II), or directly through a myofascial sleeve within the muscle (type III). The obliquus capitis inferior length was 5.60 ± 0.46 cm. The intersection point between the obliquus capitis inferior and the greater occipital nerve was 6.80 ± 0.68 cm caudal to the occiput and 3.56 ± 0.36 cm lateral to the midline. The thickness of the muscle at its intersection with the greater occipital nerve was 1.20 ± 0.25 cm. Loose, tight, and intramuscular connections were found in seven, 31, and two specimens, respectively. CONCLUSIONS: The obliquus capitis inferior remains relatively immobile during traumatic events, like whiplash injuries, placing strain as a tethering point on the greater occipital nerve. Better understanding of the anatomical relationship between the greater occipital nerve and the obliquus capitis inferior can be clinically useful in cases of posttraumatic occipital headaches for diagnostic and operative planning purposes.

A Novel Surgical Approach to Chronic Temporal Headaches.

The targets for the surgical treatment of temporal headaches are the zygomaticotemporal branch of the trigeminal nerve and the auriculotemporal nerve. The former is often accessed by means of an endoscopic brow approach or potentially by laterally extending a transpalpebral incision. An established surgical approach, the Gillies incision, was modified to access the zygomaticotemporal nerve, as it was felt to combine the advantages of the traditional techniques. Nineteen patients underwent zygomaticotemporal nerve decompression and neuroplasty or neurectomy and muscle implantation using this surgical approach. A 3.5-cm incision was made behind the anterior, temporal hairline and the zygomaticotemporal branch of the trigeminal nerve was approached directly, remaining superficial to the deep temporal fascia. Each patient was assessed preoperatively and postoperatively with regard to the frequency, duration, and severity of their symptoms to calculate a Migraine Headache Index score. All evaluations were performed at least 1 year postoperatively. The mean preoperative Migraine Headache Index score was 131.7 and the mean postoperative score was 52 (p < 0.0001). There were no surgical complications. There appeared to be no differences between those patients that had decompression and neuroplasty versus those that underwent neurectomy and implantation, as both groups experienced significant reductions in Migraine Headache Index scores following the procedure. The anterior temporal approach to the zygomaticotemporal nerve is both safe and effective. The advantages of this approach include a hidden scar, the ability to directly manipulate the nerve for transection or preservation, and access to the auriculotemporal nerve through the same incision.

Anatomic and Compression Topography of the Lesser Occipital Nerve.

BACKGROUND: The surgical treatment of occipital headaches focuses on the greater, lesser, and third occipital nerves. The lesser occipital nerve (LON) is usually transected with relatively limited available information regarding the compression topography thereof and how such knowledge may impact surgical treatment. METHODS: Eight fresh frozen cadavers were dissected focusing on the LON in relation to 3 clinically relevant compression zones. The x axis was a line drawn through the occipital protuberance (OP) and the y axis, the posterior midline (PM). In addition, a prospectively collected cohort of 36 patients who underwent decompression of the LON is presented with their clinical results, including migraine headache index scores. RESULTS: The LON was found in compression zone 1, with a mean of 7.8 cm caudal to the OP and 6.3 cm lateral to the PM. The LON was found at the midpoint of compression zone 2, with an average of 5.5 cm caudal to the OP and 6.2 cm lateral to the PM. At compression zone 3, the medial-most LON branch was located approximately 1 cm caudal to the OP and 5.35 cm lateral to the PM, whereas the lateral-most branch was identified 1 cm caudal to the OP and 6.5 cm lateral to the PM. Of the 36 decompression patients analyzed, only 5 (14%) required neurectomy as the remainder achieved statistically significant improvements in migraine headache index scores postoperatively. CONCLUSION: The knowledge of LON anatomy can aid in nerve dissection and preservation, thereby leading to successful outcomes without requiring neurectomy.

In vitro demonstration of breast cancer tumor cell sub-populations based on interleukin-1/tumor necrosis factor induction of interleukin-8 expression.

Interleukin-8 (IL-8) has been identified as an angiogenesis factor (AF) as well as a tumor cell chemotactic factor and mitogen. Recent in vivo studies have demonstrated the expression of IL-8, IL-1 and TNF, as well their receptors, on various sub-populations of tumor cells in human breast cancer (HBC). Since pro-inflammatory cytokines such as IL-1 and TNF are known inducers of IL-8 in non-tumor cells, we hypothesize that IL-1/TNF may act as an IL-8 inducer in HBC, and thus enhance HBC tumor progression. To begin to test this hypothesis, we evaluated the ability of: a) human breast cancer cell lines (BCC) and normal human breast epithelial cell lines (BEC) to produce IL-8 in vitro; and b) IL-1 and TNF to regulate the expression of IL-8. In general, basal IL-8 expression was low in all 8 cell lines examined. TNF-alpha and TNF-beta induced a 3- to 24-fold increase in IL-8 protein expression of BEC, and a 2- to 8-fold increased IL-8 expression in estrogen-independent BCC cell lines and no significant IL-8 expression in estrogen-dependent cell lines. Conversely, IL-1alpha and IL-1beta, induced a 5- to 104-fold stimulation of BEC and a 330 to 1,138-fold increase in IL-8 expression in estrogen independent BCC. These observations demonstrate the ability of HBC cells to produce IL-8 in vitro and further indicate that IL-1 is a potent inducer of IL-8 expression by BEC and BCC. Furthermore, this in vitro data support the hypothesis, that within the HBC tumor microenvironment, tumor cells exist that respond to pro-inflammatory cytokine (IL-1) stimulation (i.e. MDA-MB-231) and those that do not (i.e. MCF-7). Additionally, HBC tumor cell lines that can be induced to express high levels of IL-8 tend to be associated with a more aggressive phenotype.

Matrix metalloproteinases and the ontogeny of scarless repair: the other side of the wound healing balance.

Early gestation mammalian fetuses possess the remarkable ability to heal cutaneous wounds in a scarless fashion. Over the past 20 years, scientists have been working to decipher the mechanisms underlying this phenomenon. Much of the research to date has focused on fetal correlates of adult wound healing that promote fibrosis and granulation tissue formation. It is important to remember, however, that wound repair consists of a balance between tissue synthesis, deposition, and degradation. Relatively little attention has been paid to this latter component of the fetal wound healing process. In this study, we examined the ontogeny of ten matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in nonwounded fetal rat skin and fibroblasts as a function of gestational age. We used a semiquantitative polymerase chain reaction protocol to analyze these important enzymes at time points that represent both the scarless and scar-forming periods of rat gestation. The enzymes evaluated were collagenase-1 (MMP-1), stromelysin-1 (MMP-3), gelatinase A (MMP-2), gelatinase B (MMP-9), membrane-type matrix metalloproteinases (MT-MMPs) 1, 2, and 3, and TIMPs 1, 2, and 3. Results demonstrated marked increases in gene expression for MMP-1, MMP-3 and MMP-9 that correlated with the onset of scar formation in nonwounded fetal skin. Similar results were noted in terms of MMP-9 gene expression in fetal fibroblasts. These results suggest that differences in the expression of these matrix metalloproteinases may have a role in the scarless wound healing phenotype observed early in fetal rat gestation. Furthermore, our data suggest that the differential expression of gelatinase B (MMP-9) may be mediated by the fetal fibroblasts themselves.

Rescue of an in vitro palate nonfusion model using interposed embryonic mesenchyme.

The authors previously established an in vitro palate nonfusion model on the basis of a spatial separation between prefusion embryonic day 13.5 mouse palates (term gestation, 19.5 days). They found that an interpalatal separation distance of 0.48 mm or greater would consistently result in nonfusion after 4 days in organ culture. In the present study, they interposed embryonic palatal mesenchymal tissue between embryonic day 13.5 mouse palatal shelves with interpalatal separation distances greater than 0.48 mm in an attempt to "rescue" this in vitro palate nonfusion phenotype. Because no medial epithelial bilayer (i.e., medial epithelial seam) could potentially form, palatal fusion in vitro was defined as intershelf mesenchymal continuity with resolution of the medial edge epithelia bilaterally. Forty-two (n = 42) palatal shelf pairs from embryonic day 13.5 CD-1 mouse embryos were isolated and placed on cell culture inserts at precisely graded distances (0, 0.67, and 0.95 mm). Positive controls consisted of shelves placed in contact (n = 6). Negative controls consisted of shelves placed at interpalatal separation distances of 0.67 mm (n = 6) and 0.95 mm (n = 7) with no interposed mesenchyme. Experimental groups consisted of embryonic day 13.5 palatal shelves separated by 0.67 mm (n = 11) and 0.95 mm (n = 12) with interposed lateral palatal mesenchyme isolated at the time of palatal shelf harvest. Specimens were cultured for 4 days (n = 19) or 10 days (n = 23), harvested, and evaluated histologically. All positive controls at 4 and 10 days in culture showed complete histologic palatal fusion. All negative controls at 4 days and 10 days in culture remained unfused. Five of six palatal shelves separated at 0.67 mm interpalatal separation distance with interposed mesenchyme were fused at 4 days, and all five were fused at 10 days. At an interpalatal separation distance of 0.95 mm with interposed mesenchyme (n = 12), no palates (zero of four) were fused at 4 days, but seven of eight were fused at 10 days. These data suggest that nonfused palatal shelves can be "rescued" with an interposed graft of endogenous embryonic mesenchyme to induce fusion in vitro.

Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing.

The endothelium is a metabolically active secretory tissue, capable of responding to a wide array of environmental stimuli. Hypoxia and vascular endothelial growth factor (VEGF) are two components of the putative fracture microenvironment. This study investigated the role of hypoxia and VEGF on endothelial cell activation as it relates to the bone repair process. It was hypothesized that endothelial cells may have an important osteogenic role in fracture healing through the production of bone morphogenetic protein-2 (BMP-2), an osteogenic cytokine at the fracture site. Therefore, BMP-2 mRNA and protein expression in endothelial cells under hypoxia and/or VEGF treatment was studied. The authors observed a 2-fold to 3-fold up-regulation of BMP-2 mRNA expression in bovine capillary endothelial cells and human microvascular endothelial cells stimulated with hypoxia or rhVEGF. Furthermore, the combined effects of hypoxia and rhVEGF appeared to be additive on BMP-2 mRNA expression in bovine capillary endothelial cells. Actinomycin D and cycloheximide studies suggested that the increased mRNA expression was transcriptionally regulated. BMP-2 protein expression was up-regulated after 24 and 48 hours of treatment with either hypoxia or rhVEGF in bovine capillary endothelial cells. Surprisingly, the data suggest that endothelial cells may play not only an angiogenic role but also an osteogenic role by a direct stimulation of the osteoblasts, through the enhanced expression of a potent osteogenic factor, BMP-2, at the fracture site.

Denervation of the periosteal origin of the adductor muscles in conjunction with adductor fasciotomy in the surgical treatment of refractory groin pull.

BACKGROUND: The purpose of this study was to determine whether resection of the nerve that innervates the origin of the adductor muscle group in addition to an adductor fasciotomy will decrease pain and improve function in patients with a chronic "groin pull." METHODS: The authors conducted a retrospective multicenter chart review of 12 patients presenting with refractory groin pull. In two patients, the problem was bilateral. There were eight female and four male patients. Injuries were related to sports (n=6), gynecologic procedures (n=3), and other injuries (n=3). Surgery included adductor fasciotomy plus resection of a nerve to the periosteal origin of the adductor muscles. Cadaver dissections were performed to identify the nerve's origin. RESULTS: In 13 of the 14 patient specimens, nerves were identified histologically: each of the five cadaver dissections demonstrated the anterior branch of the obturator nerve to be this nerve's origin. At a mean of 16.7 months after surgery, 11 of the 12 patients (92 percent) and 13 of the 14 limbs (93 percent) responded with relief of pain and improved activities of daily living. Of the 14 patients, eight had an excellent result (67 percent), three had a good result (25 percent), and one experienced a failure (7 percent). CONCLUSIONS: Chronic impairment related to a groin pull injury may be considered caused by a contracture of the adductor muscle group, which can be treated with fasciotomy. A branch of the obturator nerve is shown to innervate the origin of these muscles, and denervation can be performed simultaneously with fasciotomy, improving pain and function.