Neural Interconnections of Extracranial Nerves in Headache Surgery: Anatomical Landmarks and Clinical Implications - A Review of Literature.

Headache disorders (HD) remain a nationwide challenge for the US healthcare system affecting nearly 60% of the US population. Surgical deactivation of the peripheral trigger site, also referred to as headache surgery, represents an effective treatment for patients with refractory HD pain or non-response to pharmacological regimes. Research stemming from other surgical specialties has underlined the clinical relevance of neural interconnections in refining diagnostic algorithms, adapting surgical techniques, and improving overall patient outcomes. While different HD trigger points have been identified, there is a paucity of studies discussing these mostly sensory neural interconnections between these trigger points in a comprehensive fashion. Herein, we aim to provide an overview of the specific nerves involved in HD and synthesize the current literature on HD nerve interconnections to, ultimately, deduce clinical implications. Overall, this line of research may help refine the perioperative workflow and enhance HD patient care.

Letter to the Editor: Insights into migraine surgery - An ACS-NSQIP data analysis over a 13- year period.

We demonstrate the safety of MS based on big data database research and outline the clinical relevance of white female migraineurs affected by menstrual migraines.

Letter to the Editor: The Case for Publicly Funded Headache Surgery in Germany.

Headache surgery has become a considerable therapeutic option in headache treatment and is of rising interest in the German medical sector. This viewpoint outlines the need for reimbursement of headache surgery in the German healthcare system and demonstrates its cost-effectiveness. Using state-of-the-art patient selection algorithms, the authors found headache surgery to be cost-effective within 7.2 to 6.3 years. Of note, the approach presented is not limited to the German healthcare system.

Migraine: A look down the nose.

BACKGROUND: Studies have suggested that contact between opposing mucosal surfaces in the nasal wall and cavity can be a target of the surgical treatment of migraines. Unfortunately, not enough is known about the role of nasal pathology in the pathogenesis of this condition. The co-existence of further rhinological disorders can be an impediment to defining the cause and effect of anatomical variants. The authors compared the MRI scans of migraine- and non-migraine patients (MPs and NMPs, respectively) to determine the prevalence of such mucosal contact points in order to extrapolate whether there is a significant association with migraines. METHODS: Coronal and axial MRI brain scans of 522 patients (412 migraineurs and 110 non-migraineurs) were analysed for the prevalence of anatomical variations of the nasal cavity, e.g. concha bullosa, septal deviations, mucosal swelling and contact points. RESULTS: The results showed no significant difference between MPs and NMPs patients for any of the parameters examined. Moreover, 87% MPs and 79% NMPs had at least one contact point. The most frequent contact point was between the middle turbinate and the septum, observed in 54% of MPs and 45% of NMPs. CONCLUSIONS: Contact points with the nasal mucosa are highly prevalent in both MPs and NMPs. Although a contact point does not cause a migraine in the absence of the disease, the concomitant presence of migraine and contact points can trigger an attack, and therefore, it is necessary to differentiate or exclude a rhinological disorder in these patients.

Influence of antiseptics on microcirculation after neuronal and receptor blockade.

The topical application of the antiseptics octenidine and polyhexanide on wounds seems to improve microcirculation. These two antiseptics were tested in combination with neuronal inhibition and sympathethic receptor blockade to verify these findings, explore the influence of ß blockers on these microcirculative effects, and find out the principle of operation. Investigations were carried out on a standardised cremaster muscle model in rats (n = 66). The tested antiseptics, octenidine and polyhexanide were investigated alone (n = 12) and in combination with bupivacaine (n = 12), metoprolol (n = 12), phentolamine (n = 12) and surgical denervation (n = 12). Physiological saline was used for control (n = 6). The arteriolar diameter and functional capillary density (FCD) were investigated via trans-illumination microscopy before, as well as 60 and 120 minutes after application. Polyhexanide caused a significant increase in arteriolar diameter (86·5 ± 3·8 µm versus 100·0 ± 3·6 µm) and, like octenidine (7·2 ± 0·7 n/0·22 mm(2) versus 11·6 ± 0·6 n/0·22 mm(2) ), in FCD (9·2 ± 0·5 versus 12·6 ± 0·9) as well. When the antiseptics are used in combination with bupivacaine, metoprolol, phentolamine or surgical sympathectomy, these effects were eliminated or inverted. Assessing the results of the different blockades in combination with polyhexanide, we surmise that the antiseptic polyhexanide acts on the microcirculation mainly by blocking α receptors. This study shows that polyhexanide and octenidine improve muscular perfusion. Interestingly, the benefit of polyhexanide and octenidine on muscular perfusion is eliminated when the antiseptics are combined with other vasoactive agents, especially ß blockers.

Influence of receptor antagonists, local anesthetics, and denervation on microcirculation.

OBJECTIVE: Impaired microcirculation is one of the most important factors in delayed wound healing. The aim of the study was to investigate the influence of chemical and surgical interruption of sympathetic nerve fibers and α- and ß-receptors blockers on muscular microcirculation. METHODS: The experiment was performed on a standardized cremaster muscle model of male Wistar rats (n=51). Microcirculation was recorded via transillumination microscopy on each of the 4 test groups and in a control group before and after their respective treatments with one of the following: topical application of bupivacaine, metoprolol, phentolamine, or surgical denervation. The arteriolar diameter and functional capillary density (FCD) as parameter for tissue perfusion were assessed. RESULTS: The α-blocker phentolamine was the only agent that caused a significant dilation of the arteriolar diameter (76.6 ± 6.9 vs 100.0 ± 12.0 µm). However, like bupivacaine, metoprolol, and the surgical sympathectomy, it did not improve FCD as a parameter for tissue perfusion. The strongest vasoconstriction (35.9 ± 4.3 vs 28.6 ± 4.0) and impairment of the FCD (10.0 ± 0.7 vs 4.1 ± 0.9) was induced by the ß-blocker metoprolol. CONCLUSIONS: This study shows that phentolamine could be an agent for dilating arteriolar diameter, but it did not improve FCD. Whereas the other agents, including sympathectomy, did not alter arteriolar diameter, the ß-blocker worsened both investigated parameters. Our results raise the question whether ß-blockers negatively influence microcirculation. Therefore, further studies are needed to investigate the potential adverse effects of ß-blockers on wound healing.

The du Bois sign.

According to the current literature, the term "du Bois sign" characterizes the condition of a shortened fifth finger as a symptom of congenital syphilis, Down syndrome, dyscrania, and encephalic malformation. Modern medical dictionaries and text books attribute the eponym to the French gynecologist Paul Dubois (1795-1871). Yet, a literature analysis revealed incorrect references to the person and unclear definitions of the term. Our findings showed that the origin of the term is based on observations made by the Swiss dermatologist Charles du Bois (1874-1947) in connection with congenital syphilis. In addition, a further eponymical fifth finger sign is closely associated with the du Bois sign. In conclusion, the du Bois sign has only limited diagnostic value and is frequently occurring in the normal healthy population.

Emergency pre-hospital care of burn patients.

Intensive care and the surgical therapy of burn injuries have made significant advancements. The immediate care on the scene of the accident, however, is not uniform. There is no 'golden hour' which will decide the further clinical process. The acute estimate of the percentage of the extent of the burns is of little relevance and does not facilitate the admission to a burn unit. The emergency calculation of the volume of intravenous infusion is not advisable. The choice of transport has no discernible impact on the prognosis of the patient. Avoiding hypothermia and perceiving associated trauma can be of crucial prognostic importance in the pre-hospital care of burn patients. Detailed knowledge about the circumstances of the injury is of exceeding importance.

Expression of TNF-related apoptosis-inducing ligand (TRAIL) in keratinocytes mediates apoptotic cell death in allogenic T cells.

The objective of the present study was to evaluate the aptitude of TRAIL gene expression for inducing apoptosis in co-cultivated T-cells. This should allow preparing a strategy for the development of a durable, allogenic skin substitute based on the induction of an immune-privileged transplant. In order to counteract the significant potential of rejection in transplanted allogenic keratinocytes, we created a murine keratinocyte cell line which expressed TRAIL through stable gene transfer. The exogenic protein was localized on the cellular surface and was not found in soluble condition as sTRAIL. Contact to TRAIL expressing cells in co-culture induced cell death in sensitive Jurkat-cells, which was further intensified by lymphocyte activation. This cytotoxic effect is due to the induction of apoptosis. We therefore assume that the de-novo expression of TRAIL in keratinocytes can trigger apoptosis in activated lymphocytes and thus prevent the rejection of keratinocytes in allogenic, immune-privileged transplants.

Aetiology and treatment of a previously denervated "tennis" elbow.

The aetiology of the "tennis" elbow is still disputed and treated by numerous different operations. We report 24 patients with treatment-resistant, previously denervated epicondylitis. The revision consisted of complete decompression of the radial nerve from the lateral intermuscular septum to beyond the arcade of Frohse in 24 patients using an anterolateral access. There was a mean period of 31 (10) months between the onset of the condition and the revision. Compared with the preoperative findings, there were improvements in 19 of the 24 patients, with four patients remaining unchanged, and one patient deteriorating. If the condition has been resistant to treatment for some time, complete decompression of the radial nerve is an effective option with few complications compared with further operation on the epicondyle.

Surgical treatment of angiosarcoma of the scalp: less is more.

Angiosarcomas (AS) of the scalp are rare tumors with an extremely poor prognosis mostly affecting elderly patients. Given the special anatomic nature of the blood supply to the scalp, it must be presumed that the tumor has already spread at the time of the initial presentation. We report a simple and fast surgical procedure, which places only a minimum burden on the patient. In 19 patients, we performed a resection of the external table with the defect being covered immediately by a split skin graft. The average stay in hospital amounted to 12.2 days. The postoperative period free of recurrences was 2.7 months on average. The average survival period after resection was 17.5 months. In view of the difficult diagnosis, an often delayed therapy and the rapid formation of metastases, a time-saving procedure with a low rate of complications should be given preference over other reconstructive methods.

Specific C-reactive protein measurements in plastic surgery.

The early detection of postoperative signs of infection can help to obviate serious consequences. C-reactive protein (CRP) is a highly sensitive measure of inflammatory changes. Concise knowledge of standard concentrations of CRP after various operations would allow the differentiation between a physiological rise and the interpretation of CRP as a warning sign. The aim of this study was to establish standard curves for CRP reactivity for common operations in plastic surgery and to assess the validity of CRP as a prognostic indicator of infective complications. Four groups of 30 patients each had either breast reduction, abdominoplasty, submuscular breast augmentation or exchange of breast implants. CRP concentrations were measured once preoperatively and on eight consecutive days postoperatively. CRP peak values were found throughout postoperative days 3 to 5. Concentrations on days 2 and 7 were significantly different from day 4 (p<0.04). Patients who had no sharp decline in CRP after its peak developed complications in their future postoperative course. There was significant correlation between the amount of resected tissue and CRP concentrations (r=0.78, p<0.005). Our results suggest that knowledge of standard alterations in postoperative CRP concentrations increases the early detection of complications. No sharp decline in CRP after day 5 is a warning sign. The use of specific standard curves allows a comparative assessment of actual, individual concentrations of CRP.

Significant angiogenic potential is present in the microenvironment of muscle flaps in humans.

The purpose of this study was to determine the presence of growth factors and the quality of angiogenic potential in the wound microenvironment in different types of flaps in humans. The wound exudates from 23 flaps were processed for analysis of transforming growth factor beta1 (TGF-beta1), epidermal growth factor (EGF), interleukin 1alpha (IL-1alpha), platelet-derived growth factor-AB (PDGF-AB), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1) by enzyme-linked immunosorbent assay (ELISA) or radio immuno assay (RIA). Angiogenic activity of wound fluid from latissimus flaps was determined by thymidine incorporation in porcine microendothelial cells exposed to various concentrations of wound fluid and control media. Angiogenic and matrix growth factors were altered in a linear fashion during the wound-healing process. Regression analysis provided evidence for decreasing levels of PDGF and EGF for latissimus flaps. Also, statistically significant differences of growth factor levels were found for paired comparison of flap types at different times after operation. Growth of in-vitro endothelial cells was stimulated most by 10 percent wound fluid, compared to any of the individual recombinant angiogenic factors or combinations of these factors. The data suggest that vascularized tissue flaps will promote wound healing by providing sufficient sources of growth factors in the wound environment. The particular type of flap, i.e., muscle or fasciocutaneous flap, does not seem to have an impact on growth-factor expression.

Feasibility of chemosensitivity testing in soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. METHODS: The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. RESULTS: The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. CONCLUSION: Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet.

The effect of topical tretinoin on tissue strength and skin components in a murine incisional wound model.

BACKGROUND: Vitamin A derivatives modulate the inflammatory phase in wound healing. Retinoic acid can restore decreased tensile strength and collagen content in steroid- or diabetes-impaired wounds. It is hypothesized that retinoic acid can lead to accelerated healing with improved breaking strength in unimpaired incisional wounds. MATERIALS AND METHODS: Skin incisions were made in 45 CD-1 mice. The sutured wounds were treated once daily with topical all-trans-retinoic acid 0.1% (n = 15), vehicle ointment (n = 15), or left untreated (n = 15). Skin biopsies at 1-, 2-, and 3-week intervals were examined using hematoxylin and eosin (H&E), Masson's trichrome, and immunoperoxidase staining methods. Wound breaking strength was determined by biomechanical analysis. RESULTS: Incisions treated with retinoic acid exhibited a significantly reduced breaking strength at week 1 when compared to the vehicle and control group. Histologic examination showed a prolonged inflammatory reaction with abundant deposition of granulation tissue. Despite an increased fibroplastic proliferation in the tretinoin-treated wounds, the production of collagen was diminished. CONCLUSIONS: Topical retinoic acid does not enhance the healing of unimpaired incisional wounds. The inadequate tensile strength in the early phase of the healing process is possibly the result of an increased dermal inflammatory response and the decreased collagen content. Although these adverse effects disappeared by 3 weeks postwounding, we found no discernible benefit of supplemental retinoic acid in unimpaired wounds.

Fournier's gangrene after Milligan-Morgan hemorrhoidectomy requiring subsequent abdominoperineal resection of the rectum: report of a case.

The development of Fournier's gangrene after Milligan-Morgan hemorrhoidectomy of a previously healthy 76-year-old female patient is described. After such a common surgical procedure, the patient developed full-thickness skin necrosis of the perianal region including the rectum. Immediate radical debridement was mandatory. Because of rectal involvement, a diverting sigmoid colostomy was required. The rectum had to be removed by abdominoperineal resection. This disastrous complication was completely unexpected and unpredictable after Milligan-Morgan hemorrhoidectomy because of the lack of predisposing factors.

Impact of c-Met expression on angiogenesis in soft tissue sarcomas: correlation to microvessel-density.

PURPOSE AND METHODS: The c-Met protein is significant for oncogenesis and angiogenesis within the c-Met/HGF/SF-mediator system. The aim of this study was the analysis of c-Met immunoexpression/-synthesis and microvessel density as parameters for angiogenesis and prognosis in 115 soft tissue sarcomas. RESULTS: C-Met could be detected by immunohistochemistry in 87% of sarcomas. In all, 60.9% of cases exhibited absent or faint expression of c-Met protein, and 39.1% high expression of c-Met protein with a correlation between tumor grading and c-Met immunoexpression. Using in situ hybridization with detection of c-met-mRNA-transcripts, c-Met protein synthesis within tumor cells could be demonstrated. A statistically significant correlation between c-Met immunoexpression and tumor microvessel density was found. No prognostic value of c-Met expression and microvessel density could be detected in 56 patients with clinical follow-up ( P=0.8506 and P=0.9329 for disease-free survival). CONCLUSIONS: The results underline a role of c-Met as an oncoprotein in soft tissue sarcomas with correlation between immunoexpression and grading. The statistically significant correlation between c-Met expression and microvessel density (as a parameter of tumor angiogenesis) suggests an angiogenic function of the c-Met/HGF/SF mediator system in malignant mesenchymal tumors.

Effects of desmopressin on thrombogenesis in aspirin-induced platelet dysfunction.

Aspirin causes a coagulation disorder. Desmopressin has haemostatic effects by increasing the plasma levels of coagulation factor VIII and von Willebrand factor. The precise effects of desmopressin on thrombogenesis are not known. In an in vivo model, we investigated the effect of the drug on thrombus formation and platelet function after aspirin use. Male Lewis rats weighing 250-300 g were used. Four groups with 10 animals each were formed: control, aspirin, desmopressin and aspirin + desmopressin. In each animal, the femoral artery was dissected. A thrombogenic vessel injury was created by inverting a full thickness portion of the proximal edge of the incised artery into the lumen. The following parameters were measured: maximum thrombus size, time period until maximum thrombus size was reached and overall platelet function. In addition, the thrombi generated were investigated histologically. Thrombus formation time was significantly shorter with desmopressin compared with the animals treated with aspirin (P < 0.0001) and controls (P = 0.008). Maximum thrombus size was larger in the desmopressin and desmopressin + aspirin groups when compared with the group treated with aspirin only. Overall platelet function was significantly enhanced with desmopressin compared with controls (P = 0.025) and with aspirin (P < 0.0001). The differences were confirmed histologically. In conclusion, desmopressin significantly accelerates thrombus formation in aspirin-treated animals. It can also re-establish thrombus size after the use of aspirin. Overall platelet function is significantly increased by desmopressin.