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).

Procedure

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).

References

1)

Lad SP, Patil CG, Laws ER Jr, Katznelson L. The role of inferior petrosal sinus sampling in the diagnostic localization of Cushing’s disease. Neurosurg Focus. 2007;23:E2.
2)

Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev. 1998;19:647–72.
3)

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.
4)

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/j.nec.2009.01.003. Review. PubMed PMID: 19778704.
5)

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.
6)

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.

Recurrent hemifacial spasm after microvascular decompression

Recurrent hemifacial spasm after microvascular decompression

Microvascular decompression (MVD) is a highly effective treatment for hemifacial spasm (HFS), but even if the root exit zone (REZ) from the brainstem is adequately decompressed, residual spasms after surgery or early reappearance of spasms are not uncommon 1) 2) 3) 4) 5)

Return of symptoms after a period of complete resolution of hemifacial spasm occurs in up to 10% of patients, 86% of recurrences happen within 2 yrs of surgery, and the risk of developing recurrence after 2 yrs of post-op relief is only ≈ 1% 6).


Among more than 2500 patients who underwent microvascular decompression for hemifacial spasm, 23 patients received a second MVD in the Kyung Hee University Hospital from January 2002 to December 2017. Three-dimensional time of flight magnetic resonance angiography and reconstructed imaging were used to identify the culprit vessel and its conflict upon root exit zone (REZ) of the facial nerve. They reviewed patients’ medical records and operation videos to identify the missing points of the first surgery.

8 patients had incomplete decompression, such as single-vessel decompression of multiple offending vessels. Teflon was not detected at the REZ, but was found in other locations in 12 patients. Three patients had severe adhesion with previous Teflon around the REZ. Nineteen patients had excellent surgical outcomes at immediate postoperative evaluation; 20 patients showed spasm disappearance at 1 year after surgery and 3 patients showed persistent symptoms. Neuro-vascular contacts around REZ of facial nerve were revealed on MRI of incomplete decompression and Teflon malposition patient groups. There were no clear neuro-vascular contacts in the patients with severe Teflon adhesion.

The decision on secondary MVD for persistent or recurrent spasm is troubling. However, if the neurovascular contact was observed in the MRI of the patient and there were offending vessels, the surgical outcome might be favorable 7).

References

1)

Fukushima T: Microvascular decompression for hemifacial spasm: results in 2890 cases, in Carter LP, Spetzler RF, editors. (eds): Neurovascular Surgery. New York, McGraw-Hill, 1995, pp 1133–1145
2)

Huang CI, Chen IH, Lee LS: Microvascular decompression for hemifacial spasm: analyses of operative findings and results in 310 patients. Neurosurgery 30: 53– 56; discussion 56–57, 1992.
3)

Ishikawa M, Nakanishi T, Takamiya Y, Namiki J: Delayed resolution of residual hemifacial spasm after microvascular decompression operations. Neurosurgery 49: 847– 854; discussion 854–856, 2001.
4)

Li CS: Varied patterns of postoperative course of disappearance of hemifacial spasm after microvascular decompression. Acta Neurochir (Wien) 147: 617– 620; discussion 620, 2005.
5)

Shin JC, Chung UH, Kim YC, Park CI: Prospective study of microvascular decompression in hemifacial spasm. Neurosurgery 40: 730– 734; discussion 734–735, 1997.
6)

Payner TD, Tew JM. Recurrence of Hemifacial Spasm After Microvascular Decompression. Neurosurgery. 1996; 38:686–691
7)

Park CK, Lee SH, Park BJ. Surgical Outcomes of Revision Microvascular Decompression for Persistent or Recurrent Hemifacial Spasm after Surgery: Analysis of radiological and intraoperative findings. World Neurosurg. 2019 Aug 2. pii: S1878-8750(19)32107-2. doi: 10.1016/j.wneu.2019.07.191. [Epub ahead of print] PubMed PMID: 31382068.

Craniopharyngioma Cyst Fluid

Craniopharyngioma Cyst Fluid

The dense oily fluid content of craniopharyngioma CPs is reported to cause brain tissue damage, demyelination and axonal loss in the hypothalamus; however, its exact effect on different cell types of CNS is still unexplored.

One cause of postoperative morbidity, and indeed mortality, is aseptic meningitis from spill-out of craniopharyngioma cyst contents.

Halliday and Cudlip from the John Radcliffe Hospital, developed a surgical technique for the management of large craniopharygngioma cysts extending into the third ventricle, to reduce this risk.

They described a technique of using an epidural catheter, inserted into the working channel of a neuroendoscope, to decompress the cystic portion of a craniopharyngioma cyst before opening the cyst wall widely, preventing spill-out of large volumes of cyst content into the ventricular system.

They had no cases of aseptic meningitis, nor any complications, from use of the described technique.

They believe that this is a safe and effective technique of decompression and fenestration of large suprasellar craniopharyngioma cysts that reduces rates of aseptic meningitis and the associated morbidity and mortality from this 1)


In a study, Ghosh et al. from Bangalore, collected CP cyst fluid (CCF) from mostly young patients during surgical removal and exposed it 9-10 days in vitro to the primary cultures derived from rat brain hypothalamus for 48 hours. A gradual decline in cell viability was noted with increasing concentration of CCF. Moreover, a distinct degenerative morphological transformation was observed in neurons and glial cells, including appearance of blebbing and overall reduction of the cell volume. Further, enhanced expression of Caspase-3 in neurons and glial cells exposed to CCF by immunofluorescence imaging, supported by Western blot experiment suggest CCF induced apoptosis of hypothalamic cells in culture.

They demonstrated the deleterious effects of the cyst fluid on various cell types within the tumors originating region of the brain and its surroundings for the first time. Taken together, this finding could be beneficial towards identifying the region specific toxic effects of the cyst fluid and its underlying mechanism 2).


Craniopharyngiomas (CPs) are cystic, encapsulated, slow-growing epithelial tumors. CPs can be aggressive forms invading and resorting surrounding structures of adjacent brain tissue, where Rosenthal fibers (RFs) are expressed. The aim of this study was to investigate the ultrastructure of these fibers in human biopsies and compare it with an experimental toxic model produced by the cortical infusion of the oil cyst fluid (“Oil machinery” fluid or OMF) from CPs to rats. For this purpose, the CPs from ten patients were examined by light and electron microscopy. OMF was administered to rats intracortically. Immunohistochemical detection of glial fibrillary acidic protein (GFAP) and vimentin was assessed. In both freshly obtained CPs and rat brain tissue, the presence of abundant cellular debris, lipid-laden macrophages, reactive gliosis, inflammation and extracellular matrix destruction were seen. Ultrastructural results suggest focal pathological disturbances and an altered microenvironment surrounding the tumor-brain junction, with an enhanced presence of RFs in human tumors. In contrast, in the rat brain different degrees of cellular disorganization with aberrant filament-filament interactions and protein aggregation were seen, although RFs were absent. Our immunohistochemical findings in CPs also revealed an enhanced expression of GFAP and vimentin in RFs at the peripheral, but not at the central (body) level. Through these findings we hypothesize that the continuous OMF release at the CPs boundary may cause tissue alterations, including damaging of the extracellular matrix, and possibly contributing to RFs formation, a condition that was not possible to reproduce in the experimental model. The presence of RFs at the CPs boundary might be considered as a major criterion for the degree of CPs invasiveness to normal tissue. The lack of RFs reactivity in the experimental model reveals that the invasive component of CPs is not present in the OMF, although the fluid per se can exert tissue damage 3).


Fifteen samples of cyst fluid and 14 samples of blood serum were collected from 14 patients with cystic forms of craniopharyngiomas and studied biochemically regarding total protein, albumin, immunoglobulins G and M contents, lactate and pH. Analysis of the data obtained for cyst fluids according to Felgenhauer and comparing them to those obtained for the corresponding blood sera led us to prove the hypothesis of blood-brain barrier impairment in patients with cyst formations in craniopharyngioma.

Arefyeva et al. have also revealed an elevated lactate content and decreased pH in cyst fluids compared with blood sera. Thus the pathogenesis of craniopharyngiomal cyst appears to be much more akin to those described for cysts accompanying other brain tumours than it was believed earlier 4).


A prospective study of cystic fluid in craniopharyngiomas in 10 patients was performed to correlate signal intensity on T1-weighted magnetic resonance (MR) images and biochemical analysis. Within 2 days before surgery, each patient underwent MR imaging before and after administration of gadopentetate dimeglumine. Five patients had cystic fluid lower in signal intensity than white matter, with protein levels less than 9,000 mg/dL (90.00 g/L) and no free methemoglobin. One of the five patients had the highest triglyceride concentration (84 mg/dL [0.95 mmol/L]) of all 10 patients; another of these five had the highest cholesterol concentration of all (270 mg/dL [6.98 mmol/L]). It is concluded that the increased signal intensity of cystic fluid in craniopharyngiomas on T1-weighted MR images can be caused by a protein concentration greater than or equal to 9,000 mg/dL (90.00 g/L), the presence of free methemoglobin, or both. In the ranges of concentrations measured in this study, cholesterol and triglyceride did not increase signal intensity 5).

References

1)

Halliday J, Cudlip S. A new technique of endoscopic decompression of suprasellar craniopharyngioma cyst. Acta Neurochir (Wien). 2019 Aug 4. doi: 10.1007/s00701-019-04024-x. [Epub ahead of print] PubMed PMID: 31377958.
2)

Ghosh M, Das S, Rao KVLN, Pruthi N, Ramesh VJ, Raju TR, Sathyaprabha TN. Effects of Craniopharyngioma Cyst Fluid on Neurons and Glial Cells cultured from rat brain hypothalamus. J Chem Neuroanat. 2018 Oct 16. pii: S0891-0618(18)30086-3. doi: 10.1016/j.jchemneu.2018.10.005. [Epub ahead of print] PubMed PMID: 30339791.
3)

Tena-Suck ML, Morales-Del Ángel AY, Hernández-Campos ME, Fernández-Valverde F, Ortíz-Plata A, Hernández AD, Santamaría A. Ultrastructural characterization of craniopharyngioma at the tumor boundary: A structural comparison with an experimental toxic model using “oil machinery” fluid, with emphasis on Rosenthal fibers. Acta Histochem. 2015 Oct;117(8):696-704. doi: 10.1016/j.acthis.2015.09.006. Epub 2015 Oct 26. PubMed PMID: 26515050.
4)

Arefyeva IA, Semenova JB, Zubairaev MS, Kondrasheva EA, Moshkin AV. Analysis of fluid in craniopharyngioma-related cysts in children: proteins, lactate and pH. Acta Neurochir (Wien). 2002 Jun;144(6):551-4; discussion 554. PubMed PMID: 12111487.
5)

Ahmadi J, Destian S, Apuzzo ML, Segall HD, Zee CS. Cystic fluid in craniopharyngiomas: MR imaging and quantitative analysis. Radiology. 1992 Mar;182(3):783-5. PubMed PMID: 1535894.
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