Transverse sigmoid sinus junction

Transverse sigmoid sinus junction

Anatomical localization remains integral to neurosurgery, particularly in the posterior fossa where neuronavigation is less reliable. There have been many attempts to define the location of the transverse- sigmoid sinus junction (TSSJ) using anatomical landmarks, to aid in the placement of the “strategic burr hole” during a retrosigmoid approach. There is a paucity of research allowing direct comparison of such techniques.

The asterion is not a strictly reliable landmark in terms of locating the underlying posterior fossa dura. Its location is very often directly over the transverse sigmoid sinus junction complex. Burr holes placed at the asterion may often open the bone directly over the sinus, leading to potential damage 1).

The asterion was located over the posterior fossa dura in 32% on the right and 25% on the left. Its position was over the transverse sinus or sigmoid sinus complex in 61% on the right and 66% on the left. The landmark was located above the transverse sigmoid sinus junction complex in 7% on the right and 9% on the left 2).

The top of the mastoid notch (TMN) is close to the transverse sigmoid sinus junction. The spatial position relationship between the TMN and the key points (the anterosuperior and inferomedial points of the transverse-sigmoid sinus junction, ASTS and IMTS) can be used as a novel method to precisely locate the sinus junction during lateral skull base craniotomy.

Forty-three dried adult skull samples (21 from males and 22 from females) were included in the study. A rectangular coordinate system on the lateral surface of the skull was defined to assist the analysis. According to sex and skull side, the data were divided into 4 groups: male&left, male&right, female&left and female&right. The distances from the ASTS and IMTS to the TMN were evaluated on the X-axis and Y-axis, symbolized as ASTS&TMN_x, ASTS&TMN_y, IMTS&TMN_x and IMTS&TMN_y.

Among the four groups, there was no significant difference in ASTS&TMN_x (p = 0.05) and ASTS&TMN_y (p = 0.3059), but there were significant differences in IMTS&TMN_x (p < 0.001) and IMTS&TMN_y (p = 0.01), and multiple comparisons indicated that there were significant differences between male&left and female&left both in IMTS&TMN_x (p = 0.0006) and in IMTS&TMN_y (p = 0.0081). In general, the ASTS was located 1.92 mm anterior to the TMN on the X-axis and 27.01 mm superior to the TMN on the Y-axis. For the male skulls, the IMTS was located 3.60 mm posterior to the TMN on the X-axis and 14.40 mm superior to the TMN on the Y-axis; for the female skulls, the IMTS was located 7.84 mm posterior to the TMN on the X-axis and 19.70 mm superior to the TMN on the Y-axis.

The TMN is a useful landmark for accurately locating the ASTS and IMTS 3).

Using high-resolution contrast-enhanced cranial computed tomography images, we constructed three-dimensional virtual cranial models. Fifty models (100 sides) were created from a retrospective sample of images performed in a New Zealand population. Ten methods of anatomical localization were applied to each model allowing qualitative and quantitative comparisons. The “key point” was defined as the point on the outer surface of the skull that directly overlaid the junction of the posterior fossa dura, transverse sinus (TS), and sigmoid sinus (SS). The proximity of each method to this “key point” was compared quantitatively, in addition to other descriptive observations. TSSJ localization methods analyzed included: (1) asterion; (2) emissary foramen; (3) Lang and Samii; (4) Day; (5) Rhoton; (6) Avci; (7) Ribas; (8) Tubbs; (9) Li; and (10) Teranishi.

Mean distance to the “key point” showed two tiers of accuracy, those <10 mm, and those >10 mm: Li (6.3 mm), Ribas (6.6 mm), Tubbs (6.8 mm), Teranishi (7.8 mm), Day (8.4 mm), emissary foramen (12.0 mm), Avci (13.0 mm), asterion (13.9 mm), Lang and Samii (15.6 mm), and Rhoton (17.4 mm). The asterion would most frequently overlie the TS (63%) and was often supratentorial (14%).

Each method has a unique profile of dura or sinus exposure. There are significant differences in the accuracy of localization of the TSSJ among anatomical localization methods 4).

Sixty-three patients, 29 male and 34 female, who would undergo retrosigmoid craniotomy admitted to Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical Universityfrom March to October 2019 were enrolled in the study and were divided into trial group and control group according to the computer-generated random numbers. Preoperative venous computed tomographic angiography (CTA) combined with 3-dimensional computed tomography computed tomography (3D CT) was randomly given to the patients(n=32). Asterion was used for identification of the TSSJ in the controls (n=31). The main outcome measures as postoperative complications and relevant intraoperative indicators were compared.

Incision length, craniotomy time, bone window size in trial group were shorter or smaller than those of the controls, as(6.8±0.5) cm vs (8.0±1.5) cm, (37±8) min vs (45±15) min, (8.7±1.2) cm(2) vs (10.2±2.4) cm(2) respectively, with statistical significance (all P<0.05). No statistical significance was found in bleeding amount, incidence of sinus injury and cerebrospinal fluid leakage. While incidence of neck pain was lower in case group (15.63% vs 38.71%; P=0.04) and the remission time of incisional pain in case group was shorter [(6±1) d vs (9±2) d; P=0.01].

While the technique is used, the center of the keyhole should be located at transitional place of the lateral part of the occipitomastoid suture, the retromastoid ridge and the superior nuchal line. Compared with the traditional craniotomy method marked by asterion, it has great advantages in reducing incidence of postoperative complications, craniotomy time, and the remission time of incisional pain 5).


1) , 2)

Day JD, Tschabitscher M. Anatomic position of the asterion. Neurosurgery. 1998 Jan;42(1):198-9. PubMed PMID: 9442525.

Li R, Qi L, Yu X, Li K, Bao G. Mastoid notch as a landmark for localization of the transverse-sigmoid sinus junction. BMC Neurol. 2020 Mar 27;20(1):111. doi: 10.1186/s12883-020-01688-2. PMID: 32220232; PMCID: PMC7099776.

Hall S, Peter Gan YC. Anatomical localization of the transverse-sigmoid sinus junction: Comparison of existing techniques. Surg Neurol Int. 2019 Sep 27;10:186. doi: 10.25259/SNI_366_2019. PMID: 31637087; PMCID: PMC6778333.

Wu H, Li YL, Maimaitili M, Chen LX, Mamutijiang M, Bate G, Shen YS, Lyu MY, Zhu GH. [Assessment of computed tomographic angiographysinus development combined with occipitalbone marks for the location of transverse sigmoid sinus junction]. Zhonghua Yi Xue Za Zhi. 2020 Sep 8;100(33):2618-2621. Chinese. doi: 10.3760/cma.j.cn112137-20191210-02695. PMID: 32892609.

Bilateral inferior petrosal sinus sampling

Bilateral inferior petrosal sinus sampling

Inferior petrosal sinus sampling (IPSS) is an invasive procedure in which adrenocorticotropic hormone (ACTH) levels are sampled from the veins that drain the pituitary gland; these levels are then compared with the ACTH levels in the peripheral blood to determine whether a pituitary tumor (as opposed to an ectopic source of ACTH) is responsible for ACTH-dependent Cushing syndrome. IPSS can also be used to establish on which side of the pituitary gland the tumor is located.

Bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold standard test for anatomical localization for Cushing’s disease where radiology has been inconclusive 1).

In a metaanalysis of 21 studies, the overall sensitivity and specificity of BIPSS were found to be 96% and 100% respectively 2).

Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and bilateral inferior petrosal sinus sampling (BIPSS) is considered gold standard in this regard. Stimulation using corticotropin releasing hormone (CRH) improves the sensitivity of BIPSS.

In essence, it tests to see the source of the raised ACTH levels in a patient with diagnosed Cushing’s syndrome and high or normal serum ACTH levels. The inferior petrosal sinus is where the pituitary gland drains. Therefore, a sample from here showing raised ACTH compared to the periphery suggests that it is a pituitary cause of Cushing’s, i.e. Cushing’s disease. Equivocal levels of ACTH indicate ectopic or Paraneoplastic Cushing’s Syndrome. The sample is usually taken after administration of Corticotropin-releasing hormone or, more recently, DDAVP, which have been shown to increase ACTH production in active ACTH-producing pituitary tumors. Increasingly, it is known as a gold-standard method for diagnosing Cushing’s disease.

To increase the sensitivity, the sampling is repeated after peripheral administration of oCRH. Following this a peak central to peripheral plasma ACTH ratio of 3 or more occurring 3-5 minutes after oCRH stimulation is highly indicative of Cushing disease.

see Inferior petrosal sinus sampling with desmopressin.

Asymmetric inferior petrosal sinuses (IPS) are not infrequently encountered during bilateral IPS sampling. There is little data on whether IPS symmetry influences success in predicting the adenoma side in patients with ACTH-dependent Cushing’s syndrome (CS).

BIPSS was performed in 38 patients with a mean age of 45 ± 15 years. The overall technical success rate was 97% for bilateral cannulation. Asymmetric IPS were observed in 11 (39%) patients with Cushing’s disease (CD). A side-to-side ACTH ratio was not significantly different between patients with symmetric outflow and those with asymmetric outflow at baseline (8.6 ± 2.7 versus 16.4 ± 6.0; P = 0.45), but ratios were significantly different after ovine corticotropin-releasing hormone (oCRH) stimulation (6.0 ± 2.5 versus 35.7 ± 22.5; P = 0.03). BIPSS correctly predicted the side of the adenoma in 25 (96%) patients with CD. Prediction was better when the venous outflow was symmetric (100%) rather than asymmetric (93%), although the difference was not significant (P = 0.42). Remission from CS was achieved in 32 patients (87%), independent of the symmetry of IPS.

Bearing in mind the sample size of this audit, asymmetric IPS at least do not seem to diminish the accuracy of diagnosis of ACTH-dependent CS, nor do they influence the clinical outcome 3).


Most often, BIPSS is performed by sampling ACTH peripherally and from both IPSs before and after CRH (Acthrel; Ben Venue Laboratories, Ohio, USA) administration. In the US, CRH is typically given at a dose of 1 μg/kg, by slow intravenous push over 30 seconds; in other countries, a typical dose is 100 μg. Conscious sedation is preferred to allow for the monitoring of symptoms suggesting complications. A 6-French sheath is advanced into the right femoral vein, and a five-French sheath into the left femoral vein. The larger sheath allows for sampling from the common femoral vein, while a 5-French catheter is in place distally. Subsequently, 3,000–5,000 units of heparin are given to prevent cavernous sinus and other venous thrombosis.

Next, 5-French Davis catheters are advanced through each femoral vein sheath into the contralateral internal jugular vein, followed by 2.8-French microcatheters, directed medially at the C1–2 level to access the orifice of the IPS 4). without entering clival veins 5). Both catheters are positioned symmetrically.

Once catheter positions are confirmed, two baseline ACTH specimens are collected from the right femoral sheath (peripheral specimen) and both IPSs. CRH is then administered peripherally. Repeat ACTH sampling from the periphery and both IPSs is obtained 3 minutes, 5 minutes, 10 minutes, and 15 minutes after the injection of CRH. Samples are collected in tubes that are placed on ice before transport to the laboratory. Upon completion of sampling, both femoral sheaths are removed, and manual compression is used to obtain hemostasis before transferring patients to the recovery room for a rest of approximately 4 hours.

Case series

Pereira et al. evaluated all patients that undergone bilateral inferior petrosal sinus sampling in a tertiary center, between January 1995 and March 2018. The probable diagnosis of Cushing’s disease was made when the basal central/peripheral gradient was>2 and/or>3 after stimulation with a corticotrophin-releasing hormone. The localization was suggested when the inter-sinus gradient was>1.4. The results obtained were compared with the post-operatory results: compatible histology and positive immunohistochemistry to adrenocorticotrophic hormone and/or the presence of criteria of cure. Sensitivity, specificity and predictive positive value were calculated.

A total of 49 patients were evaluated (75.5% female; mean age 45.4±16.3 years old). Bilateral inferior petrosal sinus sampling was compatible with Cushing’s disease in 27 out of 28 confirmed cases in histology or by criteria of cure, and was compatible with ectopic secretion in the 2 cases confirmed as ectopic secretion of adrenocorticotrophic hormone (sensitivity 96.4%; specificity 100%). The lateralization calculated was concordant with the results after surgery in 17 out of 27 patients with Cushing’s disease – predictive positive value of 63%. Magnetic resonance had a higher predictive value to lateralization – 70.0%.

Bilateral inferior petrosal sinus sampling is a safe and reliable procedure to diagnose Cushing’s disease, with great sensitivity and specificity. Nevertheless, the capacity of this procedure to lateralize the lesion inside the pituitary is limited 6).



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Andereggen L, Gralla J, Schroth G, Mordasini P, Andres RH, Widmer HR, Luedi MM, Kellner F, Beck J, Mariani L, Ozdoba C, Christ E. Influence of inferior petrosal sinus drainage symmetry on detection of adenomas in Cushing’s syndrome. J Neuroradiol. 2019 Jun 19. pii: S0150-9861(19)30233-0. doi: 10.1016/j.neurad.2019.05.004. [Epub ahead of print] PubMed PMID: 31228539.

Tomycz ND, Horowitz MB. Inferior petrosal sinus sampling in the diagnosis of sellar neuropathology. Neurosurg Clin N Am. 2009 Jul;20(3):361-7. doi: 10.1016/ Review. PubMed PMID: 19778704.

Doppman JL, Oldfield E, Krudy AG, Chrousos GP, Schulte HM, Schaaf M, Loriaux DL. Petrosal sinus sampling for Cushing syndrome: anatomical and technical considerations. Work in progress. Radiology. 1984 Jan;150(1):99-103. PubMed PMID: 6316418.

Pereira CA, Ferreira L, Amaral C, Alves V, Xavier J, Ribeiro I, Cardoso H. Diagnostic accuracy of Bilateral Inferior Petrosal Sinus Sampling: The Experience of a Tertiary Centre. Exp Clin Endocrinol Diabetes. 2019 Aug 19. doi: 10.1055/a-0981-5973. [Epub ahead of print] PubMed PMID: 31426111.
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