Stimulation of the greater occipital nerve: anatomical considerations and clinical implications.

BACKGROUND: Stimulation of the greater occipital nerve has been employed for various intractable headache conditions for more than a decade. Still, prospective studies that correlate stimulation of the greater occipital nerve with outcome of patients with respect to alleviation of headache are sparsely found in literature. OBJECTIVE: To identify anatomical landmarks for a reproducible stimulation of the greater occipital nerve. For the clinical implication, the individual response to therapy of patients with refractory chronic cluster headache undergoing occipital nerve stimulation was correlated with the postoperative localization of the electrodes and with the distribution of the stimulation field. STUDY DESIGN: Prospective observational study, approved by the local research ethics board (09-4143). SETTING: University hospital, departments of neurosurgery and neurology, institute of anatomy and radiology. METHODS: Ten formaldehyde fixed human cadavers were dissected to identify the passage of the greater occipital nerve through the trapezius muscle. The distance to the external occipital protuberance was triangulated measuring the distance of the nerve from the nuchal midline and the protuberance. Between December 2008 and December 2011, 21 consecutive patients suffering from chronic cluster headache underwent surgery in terms of bilateral occipital nerve stimulation, with electrodes placed horizontally at the level of C1. The postoperative x-rays were compared with the acquired landmarks from the anatomical study. The distribution of the stimulation field was correlated to the individual response of each patient to the therapy and prospectively analyzed with regard to reduction of daily cluster attacks and relief of pain intensity at 3 months and at last follow-up. RESULTS: The greater occipital nerve crosses the trapezius muscle at a mean distance of 31 mm below the occipital external protuberance and 14 mm lateral to the midline as found in the anatomical subjects. The electrodes were targeted at this level in all of our patients and stimulated the greater occipital nerve in all patients. Eighteen of the patients (85.7%) reported a significant reduction of the frequency of their cluster attacks and/or declined intensity of pain during the attacks. Yet, 3 of 21 patients (14.3%) did not benefit from the stimulation despite an adequate spread of the stimulation over the occiput. The spread of the stimulation-induced paraesthesias over the occiput was not correlated to a reduction of cluster attacks, to the intensity of attacks, or to the response to treatment at all. LIMITATIONS: Single center non-randomized non-blinded study. CONCLUSIONS: From our study we conclude that a reproducible stimulation of the greater occipital nerve can be achieved by placing the electrodes parallel to the atlas, at about 30 mm distance to the external occipital protuberance. The response to the stimulation is not correlated to the field width of the paraesthesia. We, therefore, consider stimulation of the main trunk of the greater occipital nerve to be more important than a large field of stimulation on the occiput. Still, an individual response to the occipital nerve stimulation cannot be predicted even by optimal electrode placement.

Advanced core decompression, a new treatment option of avascular necrosis of the femoral head--a first follow-up.

Aseptic necrosis of the femoral head (AVN) leads to destruction of the affected hip joint, predominantly in younger patients. Advanced core decompression (ACD) is a new technique that may allow better removal of the necrotic tissue by using a new percutaneous expandable reamer. A further modification is the refilling of the drill hole and the defect with an injectable, hard-setting, composite calcium sulphate (CaSO4)-calcium phosphate (CaPO4) bone graft substitute. Compression tests were performed on seven pairs of femoral cadaver bones. One femur of each pair was treated with ACD, while the opposite side remained untreated. Clinically, the postoperative outcome of 27 hips in 23 patients was performed by physical examination 6 weeks after ACD and at average follow-up of 9.69 months, and compared with the preoperative results. MRI was used to assess the removal of the necrotic tissue, any possible progression of AVN and evaluation of collapse. In the biomechanical analysis, the applied maximum compression force that caused the fracture did not significantly differ from the untreated opposite side. The overall results of postoperative physical examinations were significantly better than preoperatively. Five hips (18.5%) were converted to a total hip replacement. The follow-up MRIs of the other patients showed no progression of the necrotic area. The first follow-up results of ACD have been encouraging for the early stages of aseptic necrosis of the femoral head. In our opinion, an assured advantage is the high stability of the femoral neck after ACD, which allows quick rehabilitation.

Vascular wall-resident stem cells.

New vessels in the adult have been considered to be formed not only by angiogenesis, but also by postnatal vasculogenesis via endothelial progenitor cells (EPCs). However, it is still a matter of debate as to what extent the EPCs contribute to new vessel formation in the adult. While the role of the circulating and bone marrow-derived EPCs has intensively been studied, the contribution of the vascular wall itself was neglected for a long time. Evidence published in the last few years strongly suggests the existence of different stem and progenitor cell types in the vascular wall. Particularly, the presence of EPCs and smooth muscle progenitor cells (SMPCs) in distinct zones of the vascular wall supports the hypothesis that not only BM- or C-EPCs, but also vascular wall-resident stem cells (VW-SCs) might contribute to new vessel formation and vascular wall morphogenesis. However, the differentiation potential of the VW-SCs, e.g. whether a VW-SC is able to give rise to a complete hierarchy of vascular progenitors still remains to be studied. This review will provide a survey about the VW-SCs and their potential impact in vascular biology.

Emerging biology of vascular wall progenitor cells in health and disease.

New blood vessels are formed through angiogenesis and postnatal vasculogenesis. Thus, it is essential to identify vascular stem and progenitor cell niches and the mechanisms governing their role in blood vessel formation. Although much is known about circulating and bone marrow-derived endothelial progenitor cells (EPCs), little is known about the vascular wall as an EPC niche. Experimental evidence strongly suggests that EPCs, as well as other stem and progenitor cells, reside in distinct zones of the vessel wall, such as within the subendothelial space and in the so-called "vasculogenic zone" within the vascular adventitia. In this review, we discuss the potential implications of different types of vascular wall resident stem and progenitor cells in health and disease.

Endothelial and hematopoietic progenitor cells (EPCs and HPCs): hand in hand fate determining partners for cancer cells.

Tumor growth and metastasis need new vessel formation by angiogenesis provided by mature endothelial cells and postnatal vasculogenesis provided by endothelial progenitor cells (EPCs). Emerging data suggest a coordinated interaction between EPCs and hematopoietic progenitor cells (HPCs) in these processes. The complexity of the mechanisms governing the new vessel formation by postnatal vasculogenesis has increased by new evidence that not only bone marrow derived EPCs and HPCs seem to be involved in this process but also local progenitors residing within the vascular wall are mobilized and activated to new vessel formation by tumor cells. This review attempts to bring these systemic and local players of postnatal vasculogenesis together and to highlight their role in tumor growth and mestastasis.

Potential implications of vascular wall resident endothelial progenitor cells.

A rapidly increasing body of data suggests an essential role of endothelial progenitor cells (EPCs) in vascular regeneration, formation of new vessels in cardiovascular diseases and also in tumor vasculogenesis. Moreover, recent data obtained from clinical studies with anti-angiogenic drugs in tumor therapy or with pro-angiogenic stimuli in ischemic disorders implicate a predictive role of the number of EPCs circulating in the peripheral blood in monitoring of these diseases. However, there is still some controversial data regarding the relevance of the EPCs in vascular formation depending on models used and diseases studied. One of the essential prerequisites for a better understanding of the whole contribution of EPCs to vascular formation in adult, a process called postnatal vasculogenesis, is to identify their exact sources. We could recently discover the existence of EPCs in a distinct zone of the vascular wall of large and middle sized adult blood vessels and showed that these cells are capable to differentiate into mature endothelial cells, to form capillary sprouts in arterial ring assay and to build vasa vasorum-like structures within the vascular wall. They also can be mobilized very rapidly from the vascular wall by tumor cells. This review will discuss the functional implications of these vascular wall resident endothelial progenitor cells (VW-EPCs) in relation to those of EPCs circulating in peripheral blood or derived from the bone marrow in cardiovascular and neoplastic diseases.

Experimental modulation of cell-cell adhesion, invasiveness and differentiation in trophoblast cells.

The establishment of pregnancy in the human decisively depends on the competence of the early trophoblast to interact during implantation with (1). the uterine epithelium and subsequently (2). with the endometrial stroma and blood vessels. In the interaction with uterine epithelium cell-to-cell adhesion appears to be a critical element, involving initially (and astonishingly) apical cell poles of both epithelia. The subsequent invasion of the stroma includes both adhesive interactions with and degradation of extracellular matrix. How these different processes are regulated in detail remains largely unknown. While the invasiveness of the trophoblast is known to be regulated in local and temporal terms it has remained unclear so far whether trophoblast adhesiveness to cells and/or matrix is subject to a coupled regulation or whether both properties involve different, maybe sequentially effective, control mechanisms. It is also not known how the regulation of these activities is related to the differentiation pathways leading to the formation of noninvasive villous trophoblast serving endocrine as well as nutritive functions. This communication reviews experiments using normal cytotrophoblast cells isolated from first trimester or term placentae as well as malignant trophoblast (choriocarcinoma) cells treated with a panel of compounds known to modulate cell differentiation [retinoic acid, methotrexate, dibutyryl-cAMP, phorbol-(12-myristoyl-13-acetyl)-diester]. Parameters indicative of trophoblast differentiation [in particular chorionic gonadotrophin (hCG) secretion] as well as adhesion to uterine epithelial cells and invasion into extracellular matrix in vitro were monitored. While expression of differentiation parameters was increased by all drug treatments, adhesion to uterine epithelial cells in vitro was reduced. Modulation of invasiveness, however, followed a different pattern: while it was reduced in normal trophoblast cells it was even increased in choriocarcinoma cells with various substances. The response of cells with respect to production of extracellular matrix proteins or matrix-degrading proteinases showed a complex pattern that again lacked a stringent correlation with hCG production and adhesion, and in addition also with invasive behavior. These results suggest that adhesiveness of trophoblast to uterine epithelial cells and invasiveness into the uterine stroma (extracellular matrix) are subject to different control mechanisms. They support the view that trophoblast-endometrium interactions involve a cascade of various adhesion and migration processes whose cellular and molecular basis is complex but accessible to experimental investigation using a variety of available in vitro systems.