UptoDate: Indocyanine green videoangiography for intracranial aneurysm

Indocyanine green videoangiography for intracranial aneurysm

Indocyanine green videoangiography for intracranial aneurysm is applied in order to assess intra-operatively both aneurysm sac obliteration and vessel patency after clipping.

Although digital subtraction angiography (DSA) may be considered the gold standard for intraoperative vascular imaging, many neurosurgical centers rely only on indocyanine green videoangiography (ICG-VA) for the evaluation of clipping accuracy.

In a Systematic Review and Meta-Analysis of Riva et al., from BrusselsLeuvenBelgiumMonzaItaly and ChicagoIllinois because a proportion of mis-clippings cannot be identified with ICG-VA, this technique should still be considered complementary rather than a replacement to DSA during aneurysm surgery. Incorporating other intraoperative tools, such as flowmetry or electrophysiological monitoring, can obviate the need for intraoperative DSA for the identification of vessel stenosis. Nevertheless, DSA likely remains the best tool for the detection of aneurysm remnants 1).

Its a safe and effective modality of intraoperative blood flow assessment and reduces the incidence of postoperative ischaemic complications 2).

However, ICGV-derived data have been reported to be misleading at times. Della Puppa et al., noted that a simple intra-operative maneuver (the “squeezing maneuver”) allows the detection of deceptive ICGV data on aneurysm exclusion and allows potential clip repositioning. The “squeezing maneuver” is based on a gentle pinch of the dome of a clipped aneurysm when ICGV documents its apparent exclusion.

Data from 23 consecutive patients affected by intracranial aneurysms who underwent the “squeezing maneuver” were retrospectively analyzed. The clip was repositioned in all cases when the dyeing of the sac was visualized after the maneuver.

In 22% of patients, after an initial ICGV showing the aneurysm exclusion after clipping, the squeezing maneuver caused the prompt dyeing of the sac; in all cases the clip was consequently repositioned. A calcification/atheroma of the wall/neck was predictive of a positive maneuver (p= 0.0002). The aneurysm exclusion rate at post-operative radiological findings was 100%.

With the limits of this small series, the “squeezing maneuver” appears helpful in the intra-operative detection of misleading ICGV data, mostly when dealing with aneurysms with atheromasic and calcified walls 3).

In selected cases, endoscopic ICG angiographies (e-ICG-A) provides the neurosurgeon with information that cannot be obtained by microscopic ICG angiography (m-ICG-A). E-ICG-A is capable of emerging as a useful adjunct in aneurysm surgery and has the potential to further improve operative results 4).

Indocyanine green (ICG) videoangiography (VA) in cerebral aneurysm surgery allows confirmation of blood flow in parent, branching, and perforating vessels as well as assessment of remnant aneurysm parts after clip application. A retrospective analysis from Two hundred forty-six procedures were performed in 232 patients harboring 295 aneurysms. The patients, whose mean age was 54 years, consisted of 159 women and 73 men. One hundred twenty-four surgeries were performed after subarachnoid hemorrhage, and 122 were performed for incidental aneurysms. Single aneurysms were clipped in 185 patients, and multiple aneurysms were clipped in 47 (mean aneurysm diameter 6.9 mm, range 2-40 mm). No complications associated with ICG-VA occurred. Intraoperative microvascular Doppler ultrasonography was performed before ICG-VA in all patients, and postoperative digital subtraction angiography (DSA) studies were available in 121 patients (52.2%) for retrospective comparative analysis. In 22 (9%) of 246 procedures, the clip position was modified intraoperatively as a consequence of ICG-VA. Stenosis of the parent vessels (16 procedures) or occlusion of the perforators (6 procedures), not detected by micro-Doppler ultrasonography, were the most common problems demonstrated on ICG-VA. In another 11 procedures (4.5%), residual perfusion of the aneurysm was observed and one or more additional clips were applied. Vessel stenosis or a compromised perforating artery occurred independent of aneurysm location and was about equally common in middle cerebral artery and anterior communicating artery aneurysms. In 2 procedures (0.8%), aneurysm puncture revealed residual blood flow within the lesion, which had not been detected by the ICG-VA. In the postoperative DSA studies, unexpected small (< 2 mm) aneurysm neck remnants, which had not been detected on intraoperative ICG-VA, were found in 11 (9.1%) of 121 patients. However, these remnants remained without consequence except in 1 patient with a 6-mm residual aneurysm dome, which was subsequently embolized with coils.

Its a helpful intraoperative tool and led to a significant intraoperative clip modification rate of 15%. However, small, < 2-mm-wide neck remnants and a 6-mm residual aneurysm were missed by intraoperative ICG-VA in up to 10% of patients. Results in this study confirm that DSA is indispensable for postoperative quality assessment in complex aneurysm surgery 5).

References

1)

Riva M, Amin-Hanjani S, Giussani C, De Witte O, Bruneau M. Indocyanine Green Videoangiography in Aneurysm Surgery: Systematic Review and Meta-Analysis. Neurosurgery. 2018 Aug 1;83(2):166-180. doi: 10.1093/neuros/nyx387. PubMed PMID: 28973404.
2)

Lai LT, Morgan MK. Use of indocyanine green videoangiography during intracranial aneurysm surgery reduces the incidence of postoperative ischaemic complications. J Clin Neurosci. 2014 Jan;21(1):67-72. doi: 10.1016/j.jocn.2013.04.002. Epub 2013 Oct 1. PubMed PMID: 24090515.
3)

Della Puppa A, Rustemi O, Rossetto M, Gioffrè G, Munari M, Charbel FT, Scienza R. The “Squeezing Maneuver” in Microsurgical Clipping of Intracranial Aneurysms Assisted by Indocyanine Green Video-angiography (ICGV). Neurosurgery. 2014 Mar 3. [Epub ahead of print] PubMed PMID: 24594928.
4)

Mielke D, Malinova V, Rohde V. Comparison of Intraoperative Microscopic and Endoscopic ICG-angiography in Aneurysm Surgery. Neurosurgery. 2014 Mar 10. [Epub ahead of print] PubMed PMID: 24618802.
5)

Roessler K, Krawagna M, Dörfler A, Buchfelder M, Ganslandt O. Essentials in intraoperative indocyanine green videoangiography assessment for intracranial aneurysm surgery: conclusions from 295 consecutively clipped aneurysms and review of the literature. Neurosurg Focus. 2014 Feb;36(2):E7. doi: 10.3171/2013.11.FOCUS13475. PubMed PMID: 24484260.

UpToDate: Pediatric intracranial tumor

Pediatric intracranial tumor

Epidemiology

Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood.

The location of brain tumors in very young children differs from the posterior fossa predominance of older children. This is especially true in the first 6– 12 months of life, where supratentorial location is signicantly more common.

Approximately 20% of pediatric intracranial tumors arise from the thalamus or brainstem, with an incidence rate of 5% and 15%, respectively.

Medulloblastoma is the most common malignant pediatric intracranial tumor.

Diffuse intrinsic pontine glioma account for 10% to 25% of pediatric intracranial tumor.

Diagnosis

Bächli et al., from the Heidelberg University Hospital, Germany, report a single-institutional collection of pediatric brain tumor cases that underwent a refinement or a change of diagnosis after completion of molecular diagnostics that affected clinical decision-making including the application of molecularly informed targeted therapies. 13 pediatric central nervous system tumors were analyzed by conventional histology, immunohistochemistry, and molecular diagnostics including DNA methylation profiling in 12 cases, DNA sequencing in 8 cases and RNA sequencing in 3 cases. 3 tumors had a refinement of diagnosis upon molecular testing, and 6 tumors underwent a change of diagnosis. Targeted therapy was initiated in 5 cases. An underlying cancer predisposition syndrome was detected in 5 cases. Although this case series, retrospectiveand not population based, has its limitations, insight can be gained regarding precision of diagnosis and clinical management of the patients in selected cases. Accuracy of diagnosis was improved in the cases presented here by the addition of molecular diagnostics, impacting clinical management of affected patients, both in the first-line as well as in the follow-up setting. This additional information may support the clinical decision making in the treatment of challenging pediatric CNS tumors. Prospective testing of the clinical value of molecular diagnostics is currently underway 1).

Treatment

Malignant brain tumors represent a true therapeutic challenge in neurooncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group.

The pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications.

At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors.

Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors.

Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d’Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. *

The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae 2).

Complications

Case series

1)

Bächli H, Ecker J, van Tilburg C, Sturm D, Selt F, Sahm F, Koelsche C, Grund K, Sutter C, Pietsch T, Witt H, Herold-Mende C, von Deimling A, Jones D, Pfister S, Witt O, Milde T. Molecular Diagnostics in Pediatric Brain Tumors: Impact on Diagnosis and Clinical Decision-Making – A Selected Case Series. Klin Padiatr. 2018 Jul 11. doi: 10.1055/a-0637-9653. [Epub ahead of print] PubMed PMID: 29996150.
2)

Kalifa C, Grill J. The therapy of infantile malignant brain tumors: current status? J Neurooncol. 2005 Dec;75(3):279-85. Review. PubMed PMID: 16195802.

Uptodate: Intracranial Subependymoma

Intracranial Subependymoma

Intracranial subependymomas are rare, mostly incidentalomas and therefore did not receive much attention in previous literature.

Many supratentorial subependymomas appear to be centered in the cortex or subcortical white matter. Therefore, a lack of ventricular involvement does not exclude subependymoma from the differential diagnosis.

By being classified as benign grade I in the World Health Organization Classification of Tumors of the Central Nervous System, they are given a special status compared to the other ependymal tumors. Tumor recurrences are a rarity, spinal “drop metastases” do not occur. While etiological, pathological and therapeutic characteristics have been subject of several publications over the last few decades and have meanwhile been well studied, the imaging characteristics are much less well received 1).

Epidemiology

They occur in middle to late adulthood.

Representing approximately 10% of ependymal tumors, subependymomas most often “present” as incidental autopsy findings in the brains of the elderly.

Most frequently they arise in the fourth ventricle (50-60%), followed by the lateral ventricle (30-40%), and less frequently in the septum pellucidum and spinal cord 2) 3).

Intraparenchymal subependymomas are extremely rare; only 6 cases have been reported in English literature. All of them were located in the supratentorial region 4) 5) 6) , and there has been only one report of infratentorial subependymoma 7)

see Subependymoma of the fourth ventricle

Histology

Subependymomas are small, discrete tumors of adults lying most often at the foramen of Monro or the fourth ventricle. It is composed of clusters of ependymal and astrocyte-like cells in a dense fibrillary stroma. It is typically attached to a ventricular wall and the most common site is the fourth ventricle.

Histologically, the tumor may be either compact or microcystic, but extensive microcystic change is rarely reported.

The histogenesis of subependymomas is still a matter of debate, with candidates including subependymal glia, astrocytes, ependymal cells, or some mixture of these cells. A recent theory hypothesizes that they originate from tanycytes, which are cells normally located in the subependymal zone 8).

Clinical features

They are likely to remain asymptomatic throughout life and some were found by autopsy. If symptomatic, tumor location and size are critical factors for presentation.

Diagnosis

Subependymomas have typical image morphologic characteristics that differentiate them from tumors of other entities, however, the rare subgroup of histopathological mixtures of subependymomas with ependymal cell fractions has no distinctly different imaging properties.

Knowing the imaging characteristics of subpendymoma and their differential diagnoses is of particular importance in order to be able to decide between the necessity of follow-up controls, an early invasive diagnosis or, depending on the entity, tumor resection.

KEY POINTS:

· Subependymomas have typical imaging characteristics that are clearly distinguishable from other entities.. · Increased incidence in middle/ older aged men, most frequent localization: 4th ventricle..

· Symptomatic subependymomas, often located in lateral ventricles, are usually characterized by hydrocephalus..

· Radiological identification of mixed subependymoma with ependymal cell fractions is not possible..

· Image based differentiation from other entities is important for the procedure.. 9).

Treatment

The surgical aims are the maximal safe tumoral resection, the decompression of neural elements, and establishment of a pathological diagnosis and the restoration of normal CSF pathways. As subependymomas are low-grade lesions with low rates of cell proliferation and a benign clinical course, complete surgical removal is usually curative.

Case series

33 patients with subependymoma, including 4 patients with a mixture of subependymomas with ependymal cell fractions in terms of imaging and clinical aspects and with reference to a current literature review.

Subependymomas have typical image morphologic characteristics that differentiate them from tumors of other entities, however, the rare subgroup of histopathological mixtures of subependymomas with ependymal cell fractions has no distinctly different imaging properties.

Knowing the imaging characteristics of subpendymoma and their differential diagnoses is of particular importance in order to be able to decide between the necessity of follow-up controls, an early invasive diagnosis or, depending on the entity, tumor resection.

KEY POINTS:

· Subependymomas have typical imaging characteristics that are clearly distinguishable from other entities.. · Increased incidence in middle/ older aged men, most frequent localization: 4th ventricle..

· Symptomatic subependymomas, often located in lateral ventricles, are usually characterized by hydrocephalus..

· Radiological identification of mixed subependymoma with ependymal cell fractions is not possible..

· Image based differentiation from other entities is important for the procedure.. 10).


With the SEER-18 registry database, information from all patients with intracranial subependymoma diagnosed during 2004-2013 were extracted, including age, sex, race, occurrence of surgery, extent of primary surgery, receipt of radiation, tumor size, and follow-up data. Age-adjusted incidence rates, overall survival, and cause-specific survival were calculated. Cox proportional hazards model was used for both univariate and multivariate analyses.

Four hundred sixty-six cases were identified. The overall incidence of intracranial subependymoma is 0.055 per 100,000 person-years (95% confidence interval, 0.05-0.06). Through multivariate analysis, age <40 years (hazard ratio [HR], 0.21; P = 0.03), female sex (HR, 0.34; P = 0.03), location within ventricles or near brainstem (HR, 0.49; P = 0.04), and occurrence of surgery (HR, 0.50; P = 0.02) were significant independent positive prognostic factors. Receipt of radiation did not show a significant relationship.

Clinical factors such as younger age, female sex, and location within ventricles or near brain stem demonstrated positive relationship with overall survival. For treatment options, surgery remains a mainstay option. No support for radiation therapy was identified 11).


Forty-three cases of pathologically confirmed, surgically treated intracranial subependymoma were identified. Thus in this patient population, subependymomas accounted for approximately 0.07% of intracranial tumors (43 of an estimated 60,000). Radiologically, 79.1% (34/43) of intracranial subependymomas were misdiagnosed as other diseases. Pathologically, 34 were confirmed as pure subependymomas, 8 were mixed with ependymoma, and 1 was mixed with astrocytoma. Thirty-five patients were followed up for 3.0 to 120 months after surgery. Three of these patients experienced tumor recurrence, and one died of tumor recurrence. Univariate analysis revealed that shorter progression-free survival (PFS) was significantly associated with poorly defined borders. The association between shorter PFS and age < 14 years was almost significant (p = 0.51), and this variable was also included in the multivariate analysis. However, multivariate analysis showed showed only poorly defined borders to be an independent prognostic factor for shorter PFS (RR 18.655, 95% CI 1.141-304.884, p = 0.040). In patients 14 years of age or older, the lesions tended to be pure subependymomas located in the unilateral supratentorial area, total removal tended to be easier, and PFS tended to be longer. In comparison, in younger patients subependymomas tended to be mixed tumors involving the bilateral infratentorial area, with a lower total removal rate and shorter PFS.

Intracranial subependymoma is a rare benign intracranial tumor with definite radiological features. Long-term survival can be expected, although poorly defined borders are an independent predictor of shorter PFS. All the features that differ between tumors in younger and older patients suggest that they might have different origins, biological behaviors, and prognoses 12).


24 pathologically proved cases of intracranial subependymomas in 17 male and seven female patients with a mean age of 48.1 years. All patients were symptomatic. CT and MR images were used to characterize the size, shape, and location of the subependymomas; the degree of hydrocephalus; tumor calcification; and the density, signal, and enhancement characteristics of the tumors.

Eighteen of 24 tumors were 3 cm or more in greatest dimension. Nineteen were lobulated, and hydrocephalus was seen in 21. Fourteen were in the lateral ventricle, and 10 were in the posterior fossa. Calcifications were present in five (all fourth ventricular) and absent in 10 (all lateral ventricular) subependymomas imaged with unenhanced CT. On 18 contrast-enhanced CT scans, five of six subependymomas with heterogeneous enhancement were in the fourth ventricle, and nine of 12 tumors with minimal or no enhancement were in the lateral ventricle. Small internal foci with a signal intensity similar to that of CSF were seen on images of all 10 lateral ventricular subependymomas obtained with both T1-weighted and T2-weighted sequences. On 13 contrast-enhanced T1-weighted images, seven of eight tumors with heterogeneous enhancement were in the fourth ventricle, and all five with minimal or no enhancement were in the lateral ventricle.

Intracranial subependymomas were seen in symptomatic middle-aged adults and showed different CT and MR imaging features, depending on their anatomic location. Calcification and heterogeneous contrast enhancement were common features of fourth ventricular subependymomas showed a lack of calcification as well as minimal or no contrast enhancement of CT and MR images 13).

1)

Kammerer S, Mueller-Eschner M, Lauer A, Luger AL, Quick-Weller J, Franz K, Harter P, Berkefeld J, Wagner M. Subependymomas – Characteristics of a “Leave me Alone” Lesion. Rofo. 2018 Jun 18. doi: 10.1055/a-0576-1028. [Epub ahead of print] PubMed PMID: 29913520.

2)

Ragel BT, Osborn AG, Whang K, Townsend JJ, Jensen RL, Couldwell WT. Subependymomas: an analysis of clinical and imaging features. Neurosurgery. 2006;58:881–890. discussion 881-890.

3)

Nishio S, Morioka T, Mihara F, Fukui M. Subependymoma of the lateral ventricles. Neurosurg Rev. 2000;23:98–103.

4)

Natrella F, Mariottini A, Rocchi R, Miracco C. Supratentorial neurenteric cyst associated with a intraparenchymal subependymoma. BMJ Case Rep. 2012;2012

5)

Hankey GJ, Davies L, Gubbay SS. Long term survival with early childhood intracerebral tumours. J Neurol Neurosurg Psychiatry. 1989;52:778–781.

6)

Shuangshoti S, Rushing EJ, Mena H, Olsen C, Sandberg GD. Supratentorial extraventricular ependymal neoplasms: a clinicopathologic study of 32 patients. Cancer. 2005;103:2598–2605.

7)

Kim Y, Lee SY, Yi KS, Cha SH, Gang MH, Cho BS, Lee YM. Infratentorial and intraparenchymal subependymoma in the cerebellum: case report. Korean J Radiol. 2014 Jan-Feb;15(1):151-5. doi: 10.3348/kjr.2014.15.1.151. Epub 2014 Jan 8. Review. PubMed PMID: 24497806; PubMed Central PMCID: PMC3909849.

8)

Sarkar C, Mukhopadhyay S, Ralte AM, Sharma MC, Gupta A, Gaikwad S, Mehta VS. Intramedullary subependymoma of the spinal cord: a case report and review of literature. Clin Neurol Neurosurg. 2003;106:63–68.

9) , 10)

Kammerer S, Mueller-Eschner M, Lauer A, Luger AL, Quick-Weller J, Franz K, Harter P, Berkefeld J, Wagner M. Subependymomas – Characteristics of a “Leave me Alone” Lesion. Rofo. 2018 Jun 18. doi: 10.1055/a-0576-1028. [Epub ahead of print] PubMed PMID: 29913520.

11)

Nguyen HS, Doan N, Gelsomino M, Shabani S. Intracranial Subependymoma: A SEER Analysis 2004-2013. World Neurosurg. 2017 May;101:599-605. doi: 10.1016/j.wneu.2017.02.019. Epub 2017 Feb 15. PubMed PMID: 28232153.

12)

Bi Z, Ren X, Zhang J, Jia W. Clinical, radiological, and pathological features in 43 cases of intracranial subependymoma. J Neurosurg. 2015 Jan;122(1):49-60. doi: 10.3171/2014.9.JNS14155. PubMed PMID: 25361493.

13)

Chiechi MV, Smirniotopoulos JG, Jones RV. Intracranial subependymomas: CT and MR imaging features in 24 cases. AJR Am J Roentgenol. 1995 Nov;165(5):1245-50. PubMed PMID: 7572512.
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