How are podocytes affected in nail -- patella syndrome ? Nail -- patella syndrome is an autosomal-dominant hereditary disease named for dysplastic fingernails and toenails and hypoplastic or absent kneecaps evident in patients with the syndrome . Prognosis is determined by the nephropathy that develops in many such patients . Besides podocyte foot-process effacement , pathognomonic changes in the kidney comprise electron-lucent areas and fibrillar inclusions in the glomerular basement membrane . These characteristic symptoms are caused by mutations in the gene encoding the transcription factor LMX1B , a member of the LIM-homeodomain gene family . Comparable with the human syndrome , homozygous Lmx1b knockout mice lack patellae and suffer from severe podocyte damage . In contrast , however , podocin and the α3 and α4 chains of collagen IV are absent in the glomeruli of Lmx1b knockout mice . Further studies with podocyte-specific Lmx1b knockout mice have confirmed the importance of LMX1B in podocytes , as these mice apparently develop foot processes initially but lose them later on . We therefore conclude that LMX1B is essential for the development of metanephric precursor cells into podocytes and possibly also for maintaining the differentiation status of podocytes . LMX1B can serve as a model system to elucidate a genetic program in podocytes . For many years , the mesangial cell took the forefront of glomerular research -LRB- see , for example , -LSB- 1 , 2 -RSB- -RRB- , but its pedestal was first slowly shaken by the painstaking morphological investigations of Wilhelm Kriz -LRB- confer -LSB- 3 , 4 -RSB- for an early and late review , respectively -RRB- and finally abruptly toppled by irrefutable genetic evidence pointing towards the podocyte as a crucial cell in the glomerulus -LSB- 5 -RSB- . Meanwhile , the podocyte is firmly rooted in pathogenetic models of glomerular diseases and it is hard to imagine that it will leave again . Although mutations in WT1 , a gene encoding a transcription factor of the Cys2His2-zinc finger family , had been found responsible for the podocytopathies Denys-Drash syndrome -LSB- 6 -RSB- , WAGR syndrome -LSB- 7 -RSB- and Frasier syndrome -LSB- 8 -RSB- , the article by Karl Tryggvason 's group on the identification of mutations in NPHS1 added another dimension -LSB- 5 -RSB- . NPHS1 is mutated in patients suffering from congenital nephrotic syndrome of the Finnish type . It codes for nephrin , a component of the slit diaphragm , and therefore is an essential part of the glomerular filtration barrier -LSB- 9 -- 11 -RSB- . Since then several other genes have been cloned that when mutated lead to glomerular disease and which in the kidney are -LRB- almost -RRB- specifically expressed in podocytes . They are LMX1B -LSB- 12 -- 14 -RSB- , NPHS2 , the gene encoding podocin -LSB- 15 -RSB- ; ACTN4 , the gene encoding α-actinin-4 -LSB- 16 -RSB- ; CD2AP -LSB- 17 , 18 -RSB- and TRPC6 -LSB- 19 , 20 -RSB- . In the following years , an increasing amount of evidence has accumulated on the specific role of these proteins in the podocyte . Nephrin and podocin participate in the formation of the slit diaphragm complex , α-actinin-4 crosslinks actin filaments in podocytes , and TRPC6 belongs to a special class of cation channels . Very little , however , is known about how the podocyte-specific expression of these genes is achieved . The sparse evidence that has been published concerns WT1 , which binds to sequences in the promoter regions of the Podxl gene -LRB- encoding podocalyxin -RRB- -LSB- 21 -RSB- and of the NPHS1/Nphs1gene -LSB- 22 , 23 -RSB- . Although WT1 activates the respective reporter constructs , the induction of the endogenous NPHS1/Nphs1 gene by WT1 was described by one group -LSB- 23 -RSB- but not another -LSB- 22 -RSB- . Nail -- patella syndrome has been known for many decades as a hereditary disease and was one of the first genetic disorders for which linkage was established . In addition to the obvious limb abnormalities , nephrologic symptoms develop in ∼ 40 % of these patients over the course of several decades . On an ultrastructural level , the moth-eaten appearance of the glomerular basement membrane together with fibrillar deposits is considered typical of nail -- patella syndrome . In addition , podocytes lose their foot processes -LRB- for references , see -LSB- 24 -RSB- -RRB- . In 1998 , not only were the first mutations in the LMX1B gene published for patients suffering from nail -- patella syndrome -LSB- 12 -- 14 -RSB- , but a report also appeared on the first characterisation of the Lmx1b knock-out mouse -LSB- 25 -RSB- . A more careful analysis of the kidney phenotype in the Lmx1b knock-out mouse revealed pronounced retardation in the development of podocytes that did not elaborate foot processes and slit diaphragms . Consistent with this finding was the splitting of the glomerular basement membrane and the reduced number of endothelial fenestrations , because podocytes synthesise proteins of the glomerular basement membrane and control differentiation of glomerular endothelial cells -LSB- 26 , 27 -RSB- . Attractive explanations for these morphological defects have come from the observations that the α3 and α4 chains of collagen IV are no longer detected in the glomerular basement membrane -LRB- -LSB- 28 -RSB- and personal observations -RRB- , that the Nphs2 gene is no longer expressed in podocytes of homozygous Lmx1b knock-out mice , and that podocytes in homozygous Lmx1b knock-out mice produce less vascular endothelial growth factor -LRB- VEGF -RRB- -LSB- 26 , 27 -RSB- . Further molecular analysis demonstrated that LMX1B bound to AT-rich sequences in the first intron of the COL4A4 gene -LSB- 28 -RSB- and in the promoter region of the NPHS2 gene -LSB- 26 , 27 -RSB- . Although the model that LMX1B activates the expression of COL4A4 and NPHS2 , and that inactivating mutations in the LMX1B gene secondarily lead to the loss of collagen IV and podocin and therefore to the characteristic alterations in nail -- patella syndrome patients certainly is an attractive one , several caveats have to be mentioned as well . Firstly , we could not demonstrate activation of a reporter construct with 4.4 kbp of the NPHS2 promoter by LMX1B -LSB- 27 -RSB- , although another group showed an approximate twofold activation of the reporter gene controlled by four concatemerised LMX1B binding sites from the NPHS2 promoter -LSB- 26 -RSB- . Secondly , when we stably transfected a human cervical carcinoma cell line HeLa cells -LRB- which admittedly bears only a very remote similarity to podocytes -RRB- with an LMX1B cDNA , we found no upregulation of the endogenous NPHS2 gene -LSB- 27 -RSB- . Thirdly , podocin and the α3 and α4 chains of collagen IV were still present in glomeruli from patients with nail -- patella syndrome -LSB- 29 -RSB- . And fourthly , the constitutive podocyte-specific inactivation of Lmx1b in the mouse does not lead to the loss of podocin or collagen IV -LSB- 30 -RSB- . What do these apparently discrepant results mean ? If LMX1B already acts at a very early stage of podocyte development , specifically before the NPHS2 , COL4A3 and COL4A4 genes are turned on -LRB- by other transcription factors ? -RRB- , the podocyte will just not have reached an advanced enough stage of development to produce podocin and collagen IV . In other words , LMX1B may rather exert a permissive influence and , for example , initiate the spreading of the foot processes upon which podocin would be produced and slit diaphragms be elaborated . The constitutive podocyte-specific inactivation of Lmx1b represents a more comparable model for human nephropathy , but the mice only survive for ∼ 2 weeks after birth -LSB- 30 -RSB- , again limiting their usefulness . In those animals , podocin and collagen IV α3/α4 are still present , and it appears as if foot processes and slit diaphragms are first elaborated and then lost secondarily -LRB- Fig. 1 -RRB- . Does LMX1B therefore play a role not only for the initial development of podocytes but also in the maintenance of their differentiation status ? Clearly , more elaborate mouse models with an inducible inactivation of Lmx1b in adult animals are needed to answer this question . Such mice will also have the additional advantage of permitting the isolation of sufficient amounts of glomeruli , which can be used for DNA microarrays and identification of LMX1B target genes . Mouse genetics has already provided us with the verification of LDB1 as an interaction partner of LMX1B -LSB- 30 -RSB- , and it may in the end help us to identify a genetic hierarchy acting in podocytes by telling us what factors control the expression of LMX1B in podocytes , what other proteins LMX1B interacts with and what genes are regulated by LMX1B in this peculiar cell type . Fig. 1a -- f Ultrastructural and immunohistochemical characterisation of mice with podocyte-specific inactivation of Lmx1b . In 11-day-old mice , the podocyte-specific inactivation of Lmx1b leads to the loss of foot processes and to a thickened glomerular basement membrane -LRB- arrows in b -RRB- . However , despite the inactivation of Lmx1b , podocin and the α4 chain of collagen IV are still produced -LRB- d , f -RRB- . + / lox control mice with one wild-type and one floxed Lmx1b allele ; lox/lox mice with two floxed Lmx1b alleles ; Cre presence of the Cre transgene under control of the human NPHS2 promoter . Bars : 5 μm -LRB- a , b -RRB- , 20 μm -LRB- c -- f -RRB- . With permission from -LSB- 30 -RSB-

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B I O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

mouse model
podocyte foot process
promotor analysis


Pure endoscopic endonasal odontoidectomy : anatomical study Different disorders may produce irreducible atlanto-axial dislocation with compression of the ventral spinal cord . Among the surgical approaches available for a such condition , the transoral resection of the odontoid process is the most often used . The aim of this anatomical study is to demonstrate the possibility of an anterior cervico-medullary decompression through an endoscopic endonasal approach . Three fresh cadaver heads were used . A modified endonasal endoscopic approach was made in all cases . Endoscopic dissections were performed using a rigid endoscope , 4 mm in diameter , 18 cm in length , with 0 degree lenses . Access to the cranio-vertebral junction was possible using a lower trajectory , when compared to that necessary for the sellar region . The choana is entered and the mucosa of the rhinopharynx is dissected and transposed in the oral cavity in order to expose the cranio-vertebral junction and to obtain a mucosal flap useful for the closure . The anterior arch of the atlas and the odontoid process of C2 are removed , thus exposing the dura mater . The endoscopic endonasal approach could be a valid alternative to the transoral approach for anterior odontoidectomy . Introduction Removal of the odontoid process is a procedure often required for the treatment of the basilar impression with compression of the brain stem or cervical spinal cord due to irreducible atlanto-axial translocation . Different disorders may produce atlanto-axial dislocation such as congenital malformation , chronic inflammation , metabolic disorders and trauma . The transoral approach is the most favoured approach to the odontoid process and it is largely used for the surgical treatment of extradural and also intradural disorders of the cranio-vertebral junction -LSB- 6 -- 9 , 11 -- 13 , 15 , 16 , 22 -- 26 -RSB- . Despite the fact that such an approach provides a direct route to the odontoid process , it presents several disadvantages such as the deepness of the surgical corridor , the sometimes required splitting of the soft palate , the risk of tongue and teeth damage and , in case of dural opening , the increased risk of post-operative CSF leakage and meningitis . Based on the experience of endoscopic endonasal pituitary surgery -LSB- 3 , 17 -RSB- , some works have recently reported anatomical studies and clinical applications of a modified endoscopic endonasal approach for the removal of the dens . These studies show the potential applications of the endoscopic endonasal approach for the surgical management of suprasellar , parasellar and retroclival pathologies -LSB- 1 , 2 , 4 , 5 , 10 , 14 , 18 -- 21 -RSB- . This anatomic study describes the extended endoscopic endonasal approach to the cranio-vertebral junction , with particular attention to the reconstruction of the surgical route . Material and methods For this anatomic study , three fresh cadaver heads were dissected ; an extended endoscopic endonasal approach to the cranio-vertebral junction was performed in all cases . Endoscopic dissections were performed using a rigid endoscope -LRB- Karl Storz GmbH , Tuttlingen , Germany -RRB- , 4 mm in diameter , 18 cm in length , with 0 degree lenses . The endoscope was connected to a light source through a fiberoptic cable and to a camera fitted with 3CCD sensors . The video-camera was connected to a 21 '' monitor supporting the high resolution of the 3CCD technology . Results The procedure started with the introduction of the endoscope into a nasal vestibule through a lower trajectory as compared to the one employed for reaching the sellar region . Along such trajectory , the first structures to be visualized were the nasal septum medially , the inferior turbinate and the middle turbinate laterally . The inferior margin of the middle turbinate led to the choana which represented the main landmark of the approach . By advancing the endoscope through the choana it was possible to identify the ostium of the Eustachian tube laterally , the rhinopharynx posteriorly , the soft palate inferiorly and the inferior wall of the sphenoid sinus superiorly ; the latter representing the superior limit of the surgical approach . Angling the endoscope to the contralateral nasal cavity , it was possible to visualize the ostium of the contralateral Eustachian tube . The ostia of the two Eustachian tubes represented the lateral limits of this approach -LRB- see Fig. 1a , b -RRB- . Fig. 1a , b Entering the choana , the rhinopharinx and the Eustachian tube have been bilaterally visualized -LRB- iwsphs inferior wall of sphenoid sinus , ET Eustachian tube , Rphx rhinopharinx -RRB- In order to expose the cranio-vertebral junction the mucosa of rhinopharynx was incised along its lateral limits at the edge with the ostia of the Eustachian tube and along the inferior wall of the sphenoid sinus superiorly -LRB- see Fig. 2a -RRB- . The mucosa , the longus capitis and longus colli muscles were gently dissected downward as a single layer , thus creating a muscle-mucosal flap -LRB- see Figs. 2b and 3 -RRB- . Proceeding from the inferior wall of the sphenoid sinus to the soft palate of the lower clivus , the atlanto-occipital membrane , the anterior arch of C1 and the body of C2 were visualized . Fig. 2a The mucosa of the rhinopharynx has been incised in order to create a mucosal flap . b The muscles longus capitis and colli have been dissected together with the mucosa in order to expose the cranio-vertebral junction . -LRB- ET Eustachian tube , Rphx rhinopharinx , NS nasal septum , iwsphs inferior wall of sphenoid sinus , C clivus , aom atlanto-occipital membrane , C1 atlas , mmf muscle-mucosal flap -RRB- Fig. 3Schematic drawing showing the muscle-mucosal flap and the lower structures -LRB- iwsphs inferior wall of sphenoid sinus , ET Eustachian tube , C1 atlas , mmf muscle-mucosal flap , C2 axis , D dens -RRB- Introducing the endoscope in the oral cavity it was possible to reach the dissected mucosa of rhinopharynx and to transpose the muscle-mucosal flap into the oral cavity -LRB- see Fig. 4a , b -RRB- . Fig. 4a The muscle-mucosal flap is transposed in the oropharinx . b Schematic drawing showing the exposure of the cranio-vertebral junction after replacing the flap . -LRB- Ophx oropharynx , mmf muscle-mucosal flap , T tongue -RRB- This manoeuver permitted an adequate endonasal exposure of the cranio-vertebral junction without removing the mucosa of the rhinopharinx , which provides a useful autologous material for closure of the surgical field . Reintroducing the endoscope into the nasal cavity , the anterior arch of the atlas was removed and the dens with the apical and alar ligaments were exposed -LRB- see Fig. 5a , b -RRB- . The dens was then thinned with a microdrill , separated from the alar and apical ligaments , and finally removed -LRB- see Fig. 6a , b -RRB- . Fig. 5a The anterior arch of the atlas has been removed . b The dens has been exposed . -LRB- C clivus , aom atlanto-occipital membrane , C1 atlas , dm dura mater , al alar ligament , D dens -RRB- Fig. 6a The dens has been drilled . b After removal of the odontoid process the transverse ligament and the underling tectorial membrane are visible . -LRB- iwsphs inferior wall of sphenoid sinus , ET Eustachian tube , dm dura mater , D dens -RRB- At this point the transverse ligament was identified ; it was removed with the tectorial membrane , a double layer membrane positioned behind the transverse ligament , in order to expose the dura mater . At the end of the procedure the muscle-mucosal flap was replaced into the nasal cavity , thus closing the surgical field -LRB- see Fig. 7 -RRB- . Fig. 7The muscle-mucosal flap is replaced in the rhinopharinx -LRB- iwsphs inferior wall of sphenoid sinus , ET Eustachian tube , mmf muscle-mucosal flap -RRB- In this study , the endoscopic endonasal approach to the cranio-vertebral junction has been performed using both the one-nostril and the two-nostril technique , without removal of inferior and/or middle turbinate , nasal septum or other nasal structures . Although the procedure can be performed through only one nostril , the binostril technique provides , without any additional surgical trauma , a better manoeuverability of the surgical tools and the possibility to work with `` three hands '' . As a matter of fact , this technique permits a free-hand use of the endoscope in one nostril , held by the assistant , and the use of the other nostril or both nostrils for the insertion of the surgical instruments . Furthermore , in the case of a narrow nasal cavity , it is valuable to perform a unilateral middle turbinectomy and removal of the posterior third of the nasal septum to enlarge the surgical corridor . Discussion Different pathological disorders may produce atlanto-axial translocation with ventral compression of the brain stem or spinal cord . The most common are congenital malformations , such as Arnold Chiari malformation type II , chronic inflammation , such as rheumatoid arthritis , genetic transformation , such as Down 's syndrome and trauma , such as type II odontoid fracture . Some of these patients are candidate to the resection of the odontoid process for anterior decompression . The indication for odontoid resection is irreducible atlanto-axial subluxation , associated with severe spinal cord compression causing progressive myelopathy . The most favoured approach to the odontoid process is the transoral approach . This approach provides a direct route to the surgical field , without any neurovascular manipulation and passing through the oropharynx , without injuring major neurovascular structures . The main limitation to this approach is the difficulty of dural closure and the subsequent higher risk of CSF leak and meningitis . For this reason the trans-oral approach is mainly used for extradural lesions -LSB- 7 , 8 , 11 -- 13 , 15 , 22 -- 24 -RSB- , although some studies have reported its application for the surgical treatment of intradural pathology of the lower clivus and ventral cranio-cervical junction -LSB- 6 , 9 , 16 , 25 , 26 -RSB- . Other minor disadvantages are , however , related to this approach : the split of the soft palate and even of the hard palate is often performed in the case when rostral extension of the approach is required ; tongue swelling may occur for prolonged compression ; there is risk of damaging the teeth with retractors ; velopharyngeal insufficiency may develop ; and there is the necessity of nasal feeding in the postoperative stay . Recently , increased diffusion in the use of the endoscope for transsphenoidal pituitary surgery -LSB- 3 , 17 -RSB- led some studies to explore the possibility of applying the endoscopic endonasal approach in the surgical treatment of skull base lesions other than pituitary tumors . In recent years some works have reported anatomical studies and surgical experience in the endoscopic endonasal approach to different areas of the midline skull base , from the olfactory groove to the cranio-vertebral junction -LSB- 1 , 2 , 4 , 5 , 10 , 14 , 18 -- 21 -RSB- . Thanks to the properties of the endoscope itself , the endonasal approach provides a wider view of the surgical field and a close-up vision , when compared with the transoral microscopic approach . Furthermore , the minimal invasiveness of the endoscopic endonasal route may reduce some morbidities related to the transoral approach . In fact , it is no longer necessary to use mouth retractors , prolonged compression of the tongue or split of the soft palate , and even considering the necessity of a middle turbinectomy or removal of the posterior portion of the nasal septum to enlarge the surgical corridor , these adjunctive manoeuvres do not usually produce morbidity to the patient . These manoeuvres are often performed in the endonasal extended approaches to the area around the sella in live patients and do not cause any respiratory problems . The possibility of performing an odontoidectomy through the nose is strictly related to the level of the C1 -- C2 junction . In fact , in the case of a low junction , below the level of the hard palate , it is virtually impossible to remove the odontoid process with an endonasal approach . On the contrary , in the case of a high position of the atlas-axis junction , the dens is more easily reached and removed through the nasal cavities . Odontoidectomy may be considered one of the most complicated manoeuvres for the transoral approach , in which the split of the soft and even hard palate is often necessary . Thus , this approach could be evaluated for those cases in which a transoral removal is considered more difficult . However , this kind of approach still presents some of the main problems of the transoral approach . The first problem concerns the risk of CSF leak and subsequent meningitis . Although the endoscope , thanks to its close-up and multi-angled vision , has a greater chance of detecting an occasional CSF leak , it is quite hard to suture the dura and the nasopharynx mucosa with conventional suturing tools through the nose . For this reason , in our anatomical study , we have created a muscle-mucosal flap , comprehensive of the entire muscular and mucosal tissue covering the ventral cranio-vertebral junction . This flap , as shown , is transposed into the oral cavity during the bone 's removal and replaced in its original site at the end of the procedure . Due to the difficulty of anchoring the flap with suture , it is only distended on the defect and its borders are apposed on the corresponding lines of incision . The mucosa of the inferior wall of the sphenoid sinus could be stripped to favour the adherence of the flap and fibrin glue could be used to seal the edges . The creation of a peduncolated muscle-mucosal flap permits a more physiological reconstruction of the surgical corridor and , furthermore , the vascularization of the flap that directly continues with the oropharynx , facilitates a rapid healing . An endoscopic control should be performed one month after surgery to check the recreating integrity of the rhinopharynx mucosa . The second problem of the transoral approach concerns the stability of the cranio-vertebral junction . The removal of the odontoid process with its ligaments can destabilize the cranio-vertebral junction . The third problem concerns the haemostasis that is often difficult in the extended endonasal approaches . Bleeding control may become difficult with bipolar coagulation because the endonasal approach presents a long and narrow corridor , with a limited working space between the tips of the bipolar forceps . Nevertheless , specific bipolar forceps -LRB- TAKE-APART bipolar forceps ; Karl Storz GmbH , Tuttlingen , Germany -RRB- have been used to work through the nose in a safe and effective way as well . Conclusions This cadaver study has been performed to demonstrate the possibility of an anterior decompression of the upper cervical cord through an endoscopic endonasal approach . Similar to the transoral approach , the endoscopic endonasal approach provides a direct route to the surgical target , but it seems related to less morbidity . For clinical applications of this approach , the most common surgical problems are the risk of CSF leak and meningitis , the instability of the cervico-medullary junction and the bleeding control . The creation of a muscle-mucosal flap may represent a valid modality for closure of the surgical field . For application in live surgery , dedicate surgical instruments , such as endonasal bipolar forceps , high-speed low-profile drill and surgical guidance systems are needed . In selected cases this approach could be considered a valid alternative to the transoral microscopic approach for the resection of the odontoid process of C2 . Obviously , it should be performed only by surgeons very skilled in endoscopic endonasal surgery and in endoscopic cadaver-dissections , while cooperation in a team with ENT surgeons is recommended .

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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