Tranexamic acid for intracranial meningioma

Tranexamic acid for intracranial meningioma

Based upon Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Wijaya et al. from the Universitas Pelita Harapan, Tangerang, BantenIndonesia, Cedars-Sinai Medical Center, Los Angeles, CES University, El Poblado, Medellín, Antioquia, Colombia. collected fully published English literature on the administration of tranexamic acid for patients undergoing intracranial meningioma surgery using the keywords [“tranexamic acid” and “meningioma”] and its synonyms from Cochrane Central Register of Controlled Trials Database, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and PubMed. The primary outcome of the current study was total blood loss. The secondary outcomes include individuals requiring blood transfusionanesthesia duration, surgical duration, and complication rate. Each included study’s quality was assessed using the JADAD scale.

For qualitative and quantitative data synthesis, they included five RCTs (n = 321) with a mean age was 47.5 ± 11.9 years for the intervention group and 47.2 ± 11.9 years for the control group. The meta-analysis showed that the administration of TXA is associated with decreased total blood loss of standardized mean difference (SMD) of -1.40 (95% CI [-2.49, -0.31]), anesthetic time SMD -0.36 (95% CI [-0.63, -0.09]), and blood transfusion requirements RR 0.58 (95% CI [0.34, 0.99]).

The current study showed that TXA was associated with reduced intraoperative blood loss and intraoperative and postoperative blood transfusion. However, the studies are small. More RCT studies with a greater sample size are favorable 1).

Patients with supratentorial meningiomas and deemed suitable for surgical resection will be recruited in the trial. Patients will be randomized to receive either a single administration of 20 mg/kg TXA or a placebo of the same volume with a 1:1 allocation ratio after anesthesia induction. The primary endpoint is the cumulative incidence of early postoperative seizures within 7 days after craniotomy. Secondary outcomes include the incidence of non-seizure complications, changes in hemoglobin level from baseline, intraoperative blood loss, erythrocyte transfusion volume, Karnofsky Performance Status, all-cause mortality, length of stay, and total hospitalization cost.

Ethics and dissemination: This trial is registered at ClinicalTrial.gov and approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200224). The findings will be disseminated in peer-reviewed journals and presented at national or international conferences relevant to the subject fields.

Trial registration number: NCT04595786 2).


conducted a prospective, randomized double-blind clinical study. The patient scheduled to undergo excision of intracranial meningioma were randomly assigned to receive intraoperatively either intravenous TXA or placebo. Patients in the TXA group received an intravenous bolus of 20 mg/kg over 20 min followed by an infusion of 1 mg/kg/h up to surgical wound closure. Efficacy was evaluated based on total blood loss and transfusion requirements. Postoperatively, thrombotic complications, convulsive seizure, and hematoma formation were noted.

Ninety-one patients were enrolled and randomized: 45 received TXA (TXA group) and 46 received placebo (group placebo). Total blood loss was significantly decreased in the TXA group compared to the placebo (283 ml vs. 576 ml; P < 0.001). Transfusion requirements were comparable in the two groups (P = 0.95). The incidence of thrombotic complications, convulsive seizure, and hematoma formation were similar in the two groups.

TXA significantly reduces intraoperative blood loss but did not significantly reduce transfusion requirements in adults undergoing resection of intracranial meningioma 3).

Thirty patients aged 18-65 years undergoing elective meningioma resection surgery were given either tranexamic acid or placebo (0.9% saline), tranexamic acid at a loading dose of 20 mg/kg, and infusion of 1 mg/kg/h during surgery. The intraoperative blood loss, coagulation profile, and the surgical field using the Likert scale were assessed.

The patients in the tranexamic group had significantly decreased intraoperative blood loss compared to the placebo group (616.42 ± 393.42 ml vs. 1150.02 ± 416.1 ml) (P = 0.02). The quality of the surgical field was better in the tranexamic group (median score 4 vs. 2 on Likert Scale) (P < 0.001). Patients in the tranexamic group had an improved coagulation profile and decreased blood transfusion requirement (p=0.016). The blood collected in the closed suction drain in 24 h postsurgery was less in the tranexamic acid group compared to the placebo group (84.7 ± 50.4 ml vs. 127.6 ± 62.2 ml) (P = 0.047).

Tranexamic acid bolus followed by infusion reduces perioperative blood loss by 46.43% and blood transfusion requirement with improved surgical field and coagulation profile in patients undergoing intracranial meningioma resection surgery 4).


In the Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India, Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received an intravenous bolus of 20mg/kg over 20min followed by an infusion of 1mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements, and estimating surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in the tranexamic acid group compared to the placebo (830mlvs 1124ml; p=0.03). The transfusion requirement was less in the tranexamic acid group (p>0.05). The patients in the tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p=0.007). There were no significant differences between the groups regarding the extent of tumor removal, perioperative complications, hospital stay, or neurologic outcome. To conclude, the administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid 5).

A man in his 40s with a history of coronary artery disease previously treated with a drug-eluting stent presented for elective craniotomy and resection of an asymptomatic but enlarging meningioma. During his craniotomy, he received desmopressin and tranexamic acid for surgical bleeding. Postoperatively, the patient developed chest pain and was found to have an ST-elevation myocardial infarction (MI). Because of the patient’s recent neurosurgery, standard post-MI care was contraindicated and he was managed symptomatically in the intensive care unit. The echocardiogram on a postoperative day 1 demonstrated no regional wall motion abnormalities and an ejection fraction of 60%. His presentation was consistent with the thrombosis of his diagonal stent. He was transferred out of the intensive care unit on postoperative day 1 and discharged home on postoperative day 3 6).


Raghavendra et al. report the intraoperative use of tranexamic acid to secure complete hemostasis as a rescue measure in intracranial meningioma resection in uncontrollable bleeding 7).


Three of 13 patients with intracranial meningiomas showed the pre-and postoperative elevation of tissue-type plasminogen activator (t-PA) related fibrinolytic activity in euglobulin fractions (EFA). During the operation, two of these three patients showed a significant elevation of the level of fibrinogen degradation products and oozing in the operating field. However, oozing was not observed in the third patient who had been given tranexamic acid preoperatively. Fibrin autography revealed that a broad lytic band of mol wt 50-60 kDa, probably free t-PA, appeared in the plasma obtained from two of the three patients after the operation when EFA elevated significantly. In all patients studied, the t-PA antigen levels were normal preoperatively but increased both during and after the operation, and correlated mainly with the intensities of a lytic band of mol wt 110 kDa, probably t-PA complexed with its major inhibitor (PAI-1). These results suggest that excessive fibrinolysis can induce local hemorrhagic diathesis during operation and may be related to t-PA function in plasma 8).


1)

Wijaya JH, July J, Quintero-Consuegra M, Chadid DP. A systematic review and meta-analysis of the effects of tranexamic acid in surgical procedure for intracranial meningioma. J Neurooncol. 2023 Jan 12. doi: 10.1007/s11060-023-04237-2. Epub ahead of print. PMID: 36633801.
2)

Li S, Yan X, Li R, Zhang X, Ma T, Zeng M, Dong J, Wang J, Liu X, Peng Y. Safety of intravenous tranexamic acid in patients undergoing supratentorial meningiomas resection: protocol for a randomized, parallel-group, placebo control, non-inferiority trial. BMJ Open. 2022 Feb 2;12(2):e052095. doi: 10.1136/bmjopen-2021-052095. PMID: 35110315; PMCID: PMC8811564.
3)

Rebai L, Mahfoudhi N, Fitouhi N, Daghmouri MA, Bahri K. Intraoperative tranexamic acid use in patients undergoing excision of intracranial meningioma: Randomized, placebo-controlled trial. Surg Neurol Int. 2021 Jun 14;12:289. doi: 10.25259/SNI_177_2021. PMID: 34221620; PMCID: PMC8247750.
4)

Ravi GK, Panda N, Ahluwalia J, Chauhan R, Singla N, Mahajan S. Effect of tranexamic acid on blood loss, coagulation profile, and quality of the surgical field in intracranial meningioma resection: A prospective randomized, double-blind, placebo-controlled study. Surg Neurol Int. 2021 Jun 7;12:272. doi: 10.25259/SNI_296_2021. PMID: 34221603; PMCID: PMC8247710.
5)

Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R. Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci. 2017 Mar 7. pii: S0967-5868(16)31491-6. doi: 10.1016/j.jocn.2017.02.053. [Epub ahead of print] PubMed PMID: 28283245.
6)

Westfall KM, Ramcharan RN, Anderson HL 3rd. Myocardial infarction after craniotomy for asymptomatic meningioma. BMJ Case Rep. 2022 Dec 29;15(12):e252256. doi: 10.1136/bcr-2022-252256. PMID: 36581354; PMCID: PMC9806024.
7)

Raghavendra H, Varsha KS, Reddy MA, Kumar SS, Sunanda G, Nagarjuna T, Latha S. Rescue Measure in Giant Intracranial Meningioma Resection by Tranexamic Acid. J Neurosci Rural Pract. 2017 Aug;8(Suppl 1):S127-S129. doi: 10.4103/jnrp.jnrp_198_17. PMID: 28936089; PMCID: PMC5602238.
8)

Tsuda H, Oka K, Noutsuka Y, Sueishi K. Tissue-type plasminogen activator in patients with intracranial meningiomas. Thromb Haemost. 1988 Dec 22;60(3):508-13. PMID: 3149049.

Intracranial Aneurysm (IA)

Intracranial Aneurysm (IA)

The clinical presentation is varied, ranging from asymptomatic lesions to those presenting with major rupture

see Ruptured intracranial aneurysm.

Spontaneous intracranial hypotension diagnosis

Spontaneous intracranial hypotension diagnosis

Spontaneous intracranial hypotension diagnosis have evolved due to improved understanding of spontaneous intracranial hypotension pathophysiology and implementation of advanced myelography techniques. Farnsworth et al. synthesized recent updates and contextualize them in an algorithm for diagnosis and treatment of SIH, highlighting basic principles and points of practice variability or continued debate. This discussion includes finer points of SIH diagnosis, spontaneous cerebrospinal fluid fistula classification systems, less common types and variants of CSF leaks, Brain MRI Bern scoring for intracranial hypotension diagnosis, potential spontaneous intracranial hypotension complications, key technical considerations, and positioning strategies for different types of Dynamic CT myelography. 1).


The diagnosis of spontaneous intracranial hypotension or cerebrospinal fluid (CSF) hypovolemia syndrome requires a high index of suspicion and meticulous history taking, demonstration of low CSF pressure and/or neuroimaging features.


Diagnostic criteria of headache attributed to low cerebrospinal fluid pressure (per IHS Classification (ICHD-III)):

  1. any headache that developed in temporal relation to low CSF pressure or cerebrospinal fluid fistula or has led to its discovery

  2. low CSF pressure (< 6 cm of water) and/or evidence of CSF leakage on imaging

  3. not better accounted for by another ICHD-III

Radiographic criteria are not required for diagnosis since no characteristic findings are seen in 20– 25% of patients.

The median delay from presentation to the diagnosis of SIH is 4 months.

This delay may be detrimental to patient outcomes. Therefore, brain MRI without and with contrast is recommended in patients with new-onset orthostatic headaches.


The diagnosis requires a high index of suspicion and meticulous history taking, demonstration of low CSF pressure and/or neuroimaging features.

Intracranial hypotension is associated with simple clinical presentation, orthostatic headache, and characteristic MRI findings. Misdiagnosed, it leads to unnecessary procedures 2).

The primary diagnostic factor relies on confirmation of cerebrospinal fluid leakage based on reduced spinal fluid pressure. Determining the specific leakage site is the most important issue for effective treatment but remains a difficult task. Although CT myelogram, radionuclide cisternography, and MRI are commonly performed in the diagnosis of CSF hypovolemia, these techniques can rarely identify the precise leakage site.

Therefore, an epidural blood patch is performed in the lumbar spine in many cases.

The identification of the site of CSF leak in the spinal canal can be very challenging. In some cases, the site cannot be identified.

Magnetic resonance imaging for intracranial hypotension diagnosis

Continuous intracranial pressure monitoring is definitive for documenting abnormally negative intracranial pressures.

A 31-year-old male, presented with subacute onset moderate occipital and sub-occipital headaches precipitated by upright posture and relieved on recumbency and neck pain for 2 years. There was no trauma, cranial/spinal surgery. Clinical examination was normal and CSF opening pressure and laboratory study were normal. Magnetic resonance imaging (MRI) brain showed thin subdural hygroma. Another patient, 41-year-old male presented with 1 month of subacute onset severe bifrontal throbbing orthostatic headaches (OHs). CSF opening pressure was normal. Contrast MRI brain showed the presence of bilateral subdural hygromas, diffuse meningeal enhancement, venous distension, sagging of the brain, and tonsillar herniation. We report two cases of “spontaneous OHs” with normal CSF pressures who were successfully treated with epidural blood patching after poor response to conservative management 3).

Repeated measurements of the optic nerve sheath diameter (ONSD) using B-mode sonography were performed before treatment initiation, during medical treatment, and during a course of repeated placement of epidural blood patches.

On admission, transorbital sonography revealed a decreased ONSD of 4.1 mm on the right and 4.3 mm on the left side. After 8 months of treatment with caffeine and computed tomography-guided epidural blood patches a gradual distension of the ONSD into the normal range was bilaterally observed (right: 5.2 mm; left: 5.3 mm).

The ultrasound-based evaluation of the optic nerve sheath may be helpful in detecting CSF hypovolemia and for determination of treatment effects. This report should be seen as a basis for future investigations on the sonographic assessment of the optic nerve sheath in diagnosis and treatment of intracranial hypotension 4).

Symptomatic patients with SIH showed a significant decrease of ONSD, as assessed by ultrasound, when changing from the supine to the upright position. Ultrasound assessment of the ONSD in two positions may be a novel, non-invasive tool for the diagnosis and follow-up of SIH and for elucidating the pathophysiology of SIH 5).


1)

Farnsworth PJ, Madhavan AA, Verdoorn JT, Shlapak DP, Johnson DR, Cutsforth-Gregory JK, Brinjikji W, Lehman VT. Spontaneous intracranial hypotension: updates from diagnosis to treatment. Neuroradiology. 2022 Nov 7. doi: 10.1007/s00234-022-03079-5. Epub ahead of print. PMID: 36336758.
2)

Louhab N, Adali N, Laghmari M, Hymer WE, Ben Ali SA, Kissani N. Misdiagnosed spontaneous intracranial hypotension complicated by subdural hematoma following lumbar puncture. Int J Gen Med. 2014 Jan 15;7:71-3. doi: 10.2147/IJGM.S48656. eCollection 2014. PubMed PMID: 24470768; PubMed Central PMCID: PMC3896286.
3)

Hassan KM, Prakash S, Majumdar SS, Banerji A. Two cases of medically-refractory spontaneous orthostatic headaches with normal cerebrospinal fluid pressures responding to epidural blood patching: Intracranial hypotension versus hypovolemia and the need for clinical awareness. Ann Indian Acad Neurol. 2013 Oct;16(4):699-702. doi: 10.4103/0972-2327.120461. PubMed PMID: 24339614; PubMed Central PMCID: PMC3841635.
4)

Bäuerle J, Gizewski ER, Stockhausen Kv, Rosengarten B, Berghoff M, Grams AE, Kaps M, Nedelmann M. Sonographic assessment of the optic nerve sheath and transorbital monitoring of treatment effects in a patient with spontaneous intracranial hypotension: case report. J Neuroimaging. 2013 Apr;23(2):237-9. doi: 10.1111/j.1552-6569.2011.00640.x. Epub 2011 Sep 1. PubMed PMID: 21883624.
5)

Fichtner J, Ulrich CT, Fung C, Knüppel C, Veitweber M, Jilch A, Schucht P, Ertl M, Schömig B, Gralla J, Z’Graggen WJ, Bernasconi C, Mattle HP, Schlachetzki F, Raabe A, Beck J. Management of spontaneous intracranial hypotension – Transorbital ultrasound as discriminator. J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):650-5. doi: 10.1136/jnnp-2015-310853. Epub 2015 Aug 18. PubMed PMID: 26285586; PubMed Central PMCID: PMC4893146.

Tobacco cigarette smoking as an intracranial aneurysm risk factor

Tobacco cigarette smoking as an intracranial aneurysm risk factor

Although several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture.

Patients from a prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population.

The proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48).

Smoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification 1).


Tobacco cigarette smoking is an independent risk factor for ruptured intracranial aneurysm, and the rupture risk in current smokers is 3× higher than that of nonsmokers 2).


A dose-response relationship has been noted for the intensity and duration of smoking consumption and increased risk of IAR. As smoking is modifiable, this finding is important to managing patients with IAs to quit or reduce smoking prior to life-threatening subarachnoid hemorrhage 3)


Current cigarette smoking, smoking intensity, and smoking duration are significantly associated with ruptured IAs at presentation. However, the significantly increased risk persists after smoking cessation, and smoking cessation does not confer a reduced risk of aneurysmal subarachnoid hemorrhage beyond that of reducing the cumulative dose 4).


Intravenous thrombolysis-treated stroke patients with unruptured intracranial aneurysms were more often current smokers and had higher systolic blood pressure than the matched patients without UIAs. They were as likely to have unfavorable outcomes at 3 months but seemed less likely to achieve excellent outcomes and were more likely to have higher mRS in shift analysis 5).


1)

Schatlo B, Gautschi OP, Friedrich CM, Ebeling C, Jägersberg M, Kulscar Z, Pereira VM, Schaller K, Bijlenga P. Association of single and multiple aneurysms with tobacco abuse: an @neurIST risk analysis. Neurosurg Focus. 2019 Jul 1;47(1):E9. doi: 10.3171/2019.4.FOCUS19130. PubMed PMID: 31261132.
2) , 4)

Can A, Castro VM, Ozdemir YH, Dagen S, Yu S, Dligach D, Finan S, Gainer V, Shadick NA, Murphy S, Cai T, Savova G, Dammers R, Weiss ST, Du R. Association of intracranial aneurysm rupture with smoking duration, intensity, and cessation. Neurology. 2017 Sep 26;89(13):1408-1415. doi: 10.1212/WNL.0000000000004419. Epub 2017 Aug 30. PMID: 28855408; PMCID: PMC5649762.
3)

Feng X, Qian Z, Zhang B, Guo E, Wang L, Liu P, Wen X, Xu W, Jiang C, Li Y, Wu Z, Liu A. Number of Cigarettes Smoked Per Day, Smoking Index, and Intracranial Aneurysm Rupture: A Case-Control Study. Front Neurol. 2018 May 31;9:380. doi: 10.3389/fneur.2018.00380. PMID: 29904368; PMCID: PMC5990590.
5)

Virta JJ, Strbian D, Putaala J, Kaprio J, Korja M. Characteristics and Outcomes of Thrombolysis-Treated Stroke Patients With and Without Saccular Intracranial Aneurysms. Stroke. 2022 Oct 18. doi: 10.1161/STROKEAHA.122.040151. Epub ahead of print. PMID: 36254706.

Borden type I intracranial dural arteriovenous fistula

Borden type I intracranial dural arteriovenous fistula

Type I dural arteriovenous fistulas are supplied by a meningeal artery or arteries and drain into a meningeal vein or dural venous sinus. The flow within the draining vein or venous sinus is anterograde.

Equivalent to Cognard type I and IIa, with a favorable natural history 1) 2).

Type Ia – simple dural arteriovenous fistulas have a single meningeal arterial supply

Type Ib – more complex arteriovenous fistulas are supplied by multiple meningeal arteries The distinction between Types Ia and Ib is somewhat specious as there is a rich system of meningeal arterial collaterals. Type I dural fistulas are often asymptomatic, do not have a high risk of bleeding and do not necessarily need to be treated


A small number of Type I DAVFs will convert to more aggressive DAVFs with CVD over time. This conversion to a higher-grade DAVF is typically heralded by a change in patient symptoms. Follow-up vascular imaging is important, particularly in the setting of recurrent or new symptoms. 3).


A comparative meta-analysis was completed to evaluate the outcomes of intervention versus observation of Borden type I intracranial dural arteriovenous fistula. Outcome measures included: grade progression, worsening symptoms, death due to dural arteriovenous fistula, permanent complications other than death, functional independence (mRS 0-2), and rate of death combined with permanent complication, were evaluated. Risk differences (RD) were determined using a random effects model.

Three comparative studies combined with the authors’ institutional experience resulted in a total of 469 patients, with 279 patients who underwent intervention and 190 who were observed. There was no significant difference in dAVF grade progression between the intervention and observation arms, 1.8% vs. 0.7%, respectively (RD: 0.01, 95% CI: -0.02 to 0.04, P = 0.49), or in symptom progression occurring in 31/279 (11.1%) intervention patients and 11/190 (5.8%) observation patients (RD: 0.03, CI: -0.02 to 0.09, P = 0.28). There was also no significant difference in functional independence on follow-up. However, there was a significantly higher risk of dAVF-related death, permanent complications from either intervention or dAVF-related ICH or stroke in the intervention group (11/279, 3.9%) compared to the observation group (0/190, 0%) (RD: 0.04, CI: 0.1 to 0.06, P = 0.007).

CoIntervention of Borden Type I dAVF results in a higher risk of death or permanent complication, which should be strongly considered when deciding on the management of these lesions 4).


From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion.

Results: During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02).

Conclusion: In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction 5)


1)

Davies MA, TerBrugge K, Willinsky R, Coyne T, Saleh J, Wallace MC. The validity of classification for the clinical presentation of intracranial dural arteriovenous fistulas. J Neurosurg. 1996 Nov;85(5):830-7. doi: 10.3171/jns.1996.85.5.0830. PMID: 8893721.
2)

Strom RG, Botros JA, Refai D, Moran CJ, Cross DT 3rd, Chicoine MR, Grubb RL Jr, Rich KM, Dacey RG Jr, Derdeyn CP, Zipfel GJ. Cranial dural arteriovenous fistulae: asymptomatic cortical venous drainage portends less aggressive clinical course. Neurosurgery. 2009 Feb;64(2):241-7; discussion 247-8. doi: 10.1227/01.NEU.0000338066.30665.B2. PMID: 19190453.
3)

Shah MN, Botros JA, Pilgram TK, Moran CJ, Cross DT 3rd, Chicoine MR, Rich KM, Dacey RG Jr, Derdeyn CP, Zipfel GJ. Borden-Shucart Type I dural arteriovenous fistulas: clinical course including risk of conversion to higher-grade fistulas. J Neurosurg. 2012 Sep;117(3):539-45. doi: 10.3171/2012.5.JNS111257. Epub 2012 Jun 22. PMID: 22725983.
4)

Schartz D, Rahmani R, Gunthri A, Kohli GS, Akkipeddi SMK, Ellens NR, Romiyo P, Kessler A, Bhalla T, Mattingly TK, Bender MT. Observation versus intervention for Borden type I intracranial dural arteriovenous fistula: A pooled analysis of 469 patients. Interv Neuroradiol. 2022 Sep 13:15910199221127070. doi: 10.1177/15910199221127070. Epub ahead of print. PMID: 36113111.
5)

Nishi H, Ikeda H, Ishii A, Kikuchi T, Nakahara I, Ohta T, Sakai N, Imamura H, Takahashi JC, Satow T, Okada T, Miyamoto S. A multicenter prospective registry of Borden type I dural arteriovenous fistula: results of a 3-year follow-up study. Neuroradiology. 2022 Apr;64(4):795-805. doi: 10.1007/s00234-021-02752-5. Epub 2021 Oct 10. PMID: 34628528; PMCID: PMC8907088.

Intracranial aneurysm pathogenesis

Intracranial aneurysm pathogenesis

Until now, the exact etiology of intracranial aneurysms formation remains unclear.

Time-dependent and site-dependent morphological changes and the level of degradation molecules may be indicative of the vulnerability of aneurysm rupture 1).

Miyata et al. proposed the contribution of a structural change in an adventitia, i.e., vasa vasorum formation, to the rupture of IAs 2).

Intracranial aneurysm risk factors.

Aneurysm wall degeneration.

Saccular intracranial aneurysm rupture leads to subarachnoid hemorrhage and is preceded by chronic inflammation and atherosclerotic changes of the Saccular intracranial aneurysm wall. Increased lymphangiogenesis has been detected in atherosclerotic extracranial arteries and in abdominal aortic aneurysms, but the presence of lymphatic vessels in saccular intracranial aneurysm (sIAs) has remained unexplored. Huuska et al. studied the presence of lymphatic vessels in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), using immunohistochemical and immunofluorescence stainings for Lymphatic endothelial cells (LEC)markers. Of these LEC-markers, both extracellular and intracellular LYVE1podoplaninVEGFR-3, and Prox1-positive stainings were detected in 83%, 94%, 100%, and 72% of the 36 sIA walls, respectively. Lymphatic vessels were identified as ring-shaped structures positive for one or more of the LEC markers. Of the sIAs, 78% contained lymphatic vessels positive for at least one LEC marker. The presence of LECs and lymphatic vessels were associated with the number of CD68+ and CD163+ cells in the sIA walls, and with the expression of inflammation indicators such as serum amyloid A, myeloperoxidase, and cyclo-oxygenase 2, with the presence of a thrombus, and with the sIA wall rupture. Large areas of VEGFR-3 and α-smooth muscle actin (αSMA) double-positive cells were detected in medial parts of the sIA walls. Also, a few podoplanin and αSMA double-positive cells were discovered. In addition, LYVE-1 and CD68 double-positive cells were detected in the sIA walls and in the thrombus revealing that certain CD68+ macrophages are capable of expressing LEC markers. This study demonstrates for the first time the presence of lymphatic vessels in human sIA walls. Further studies are needed to understand the role of lymphatic vessels in the saccular intracranial aneurysm pathogenesis 3).

see Intracranial aneurysm genetics.

see Intracranial aneurysm pathophysiology.

see Intracranial aneurysm hemodynamics.

In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage.

Data suggest that macrophage-derived Matrix metalloproteinase 2 and Matrix metalloproteinase 9, may play an important role in the progression of intracranial aneurysms. The findings will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease 4).

Investigations strongly suggest that the pathophysiology is closely associated with chronic inflammation in vascular walls. Nuclear factor kappaB (NF-kappaB) has a key role in the formation and progression.

Children with Sickle Cell Disease (SCD) are at risk for developing multiple intracranial aneurysms, and a high index of suspicion must be maintained during the interpretation of routine magnetic resonance imaging or angiography of the brain 5).

Dental bacterial DNA can be found using a quantitative polymerase chain reaction in both ruptured and unruptured aneurysm walls, suggesting that bacterial DNA plays a role in the pathogenesis of cerebral aneurysms in general, rather than only in ruptured aneurysms 6).

Thrombospondin type-1 domain-containing protein 1 is a protein that in humans is encoded by the THSD1 gene.

The protein encoded by this gene contains a type 1 thrombospondin domain, which is found in thrombospondin, a number of proteins involved in the complement pathway, as well as extracellular matrix proteins. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

As illustrated by THSD1 research, cell adhesion may play a significant role in IA 7).

A study discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting evidence from two vertebrate models 8).

A report identified THSD1 mutations in familial and sporadic IA patients and shows that THSD1 loss results in cerebral bleeding in 2 animal models. This finding provides new insight into IA and subarachnoid hemorrhage pathogenesis and provides new understanding of THSD1 function, which includes endothelial cell to extracellular matrix adhesion 9).

Toll‑like receptor (TLR) 2/4 serves an important regulatory role in nerve tissue injury. However, the downstream and potential mechanisms remain to be elucidated. The present study was designed to investigate the roles of the TLR2/4‑major myeloid differentiation response gene 88 (MyD88)‑NF‑κB signaling pathway in the development of an intracranial aneurysm. The expression of TLR2, TLR4, and MyD88 in the blood of normal controls and patients with intracranial aneurysms were detected by quantitative PCR and ELISA. Human brain vascular smooth muscle cells were treated by Angiotensin II (Ang II) to evaluate the involvement of the TLR2/4‑MyD88‑NF‑κB signaling pathway in the process. The in vitro experiment was divided into four groups: The control group, an Ang Ⅱ group, an Ang Ⅱ + small interfering (si)RNA control group, and an Ang Ⅱ + TLR2‑group. Cell viability, migration, apoptosis, and expression of TLR2, TLR4, MyD88, NF‑κB, and phosphorylated (p‑)p65 expression was detected. The results demonstrated that the expression of TLR2, TLR4, MyD88, and NF‑κB at mRNA and protein levels in patients with an intracranial aneurysm was significantly higher compared with corresponding protein in normal controls (P&lt;0.05). <em>In vitro</em> experiments demonstrated that Ang Ⅱ treatment increased the cell proliferation and migration rate but reduced the apoptotic rate compared with the control (P&lt;0.05). The expression of TLR2, TLR4, MyD88, NF‑κB, and p‑p65 was significantly increased in the Ang II group (vs. control; P&lt;0.05). By contrast, TLR2‑short interfering RNA reduced the cell proliferation and migration rate and reduced the expression of TLR2, TLR4, MyD88, NF‑κB, and p‑p65 (vs. Ang Ⅱ + short interfering RNA control; P&lt;0.05). In conclusion, the data of the present study indicated that the TLR2/4‑MyD88‑NF‑κB signaling pathway is involved in the intracranial aneurysm pathogenesis 10).


Vascular smooth muscle cells

Dysfunction of vascular smooth muscle cells (VSMCs) plays a critical role in the intracranial aneurysm pathogenesis (IA). Circular RNAs (circRNAs) have been implicated by reducing microRNA (miRNA) activity. Qin et al. investigated the precise roles of circRNA ADP ribosylation factor interacting protein 2 (circ-ARFIP2, circ_0021001) in VSMC dysfunction. The levels of circ-ARFIP2, miR-338-3p and kinase insert domain receptor (KDR) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease (RNase) R and subcellular fractionation assays were used to assess the stability and localization of circ-ARFIP2, respectively. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell invasion was measured by transwell assay. Cell proliferation was gauged by 5-Ethynyl-2′-Deoxyuridine (EdU) assay. Cell migration was evaluated by transwell and wound-healing assays. Targeted correlations among circ-ARFIP2, miR-338-3p and KDR were validated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ-ARFIP2 and KDR were underexpressed and miR-338-3p was overexpressed in the arterial wall tissues of IA patients. Overexpression of circ-ARFIP2 in human umbilical artery smooth muscle cells (HUASMCs) showed a significant promotion in cell proliferation, migration and invasion. Mechanistically, circ-ARFIP2 targeted miR-338-3p, and circ-ARFIP2 regulated cell behaviors by miR-338-3p. KDR was a direct and functional target of miR-338-3p. Moreover, KDR was a downstream effector of circ-ARFIP2 function. Circ-ARFIP2 regulated KDR expression by targeting miR-338-3p.The findings demonstrated that the increased level of circ-ARFIP2 enhanced HUASMC proliferation, migration and invasion at least in part by the miR-338-3p/KDR axis 11).


Pathogenic inflammation contributes to aneurysm formation by mediating the destruction of the endothelium and the extracellular matrix and promoting pathogenic proliferation of smooth muscle cells. In mouse models, tolerance-inducing T regulatory (Treg) cells could significantly reduce the incidence and severity of aneurysms. Hence, it should be investigated why in human intracranial aneurysm (IA) patients, Treg cells failed to provide protection against aneurysm formation. In this study, the frequency and function of Treg cells in IA patients were examined. The frequency of Foxp3+ Treg cells was significantly lower in IA patients than in healthy controls. This downregulation was only specific to the Treg subset of CD4+ T cells, as the frequency of total CD4+ T cell was increased in IA patients. Subsequently, we found that the expressions of Treg-associated molecules, including Foxp3, CTLA-4, TGF-β, and IL-10, were significantly lower in Foxp3+ Treg cells from IA patients than in Foxp3+ Treg cells from healthy controls. In both healthy controls and IA patients, Foxp3+ Treg cells were distinguished into a more potent Tim-3+ subset and a less potent Tim-3- subset. The Tim-3+ subset of Foxp3+ Treg cells was significantly reduced in IA patients. Signaling via IL-2, IL-7, IL-15 and IL-21 was shown to promote Tim-3 upregulation in CD4+ and CD8+ T cells. Interestingly, we found that Tim-3 could be upregulated in Treg cells via the same mechanism, but compared to the Treg cells from healthy controls, the Treg cells from IA patients presented defects in Tim-3 upregulation upon cytokine stimulation. Together, our results demonstrated that Foxp3+ Treg cells in IA patients presented reduced function, which was associated with a defect in Tim-3 upregulation 12).


1)

Yamaguchi T, Miyamoto T, Kitazato KT, Shikata E, Yamaguchi I, Korai M, Shimada K, Yagi K, Tada Y, Matsuzaki Y, Kanematsu Y, Takagi Y. Time-dependent and site-dependent morphological changes in rupture-prone arteries: ovariectomized rat intracranial aneurysm model. J Neurosurg. 2019 Sep 13:1-9. doi: 10.3171/2019.6.JNS19777. [Epub ahead of print] PubMed PMID: 31518986.
2)

Miyata H, Imai H, Koseki H, Shimizu K, Abekura Y, Oka M, Kawamata T, Matsuda T, Nozaki K, Narumiya S, Aoki T. Vasa vasorum formation is associated with rupture of intracranial aneurysms. J Neurosurg. 2019 Aug 16:1-11. doi: 10.3171/2019.5.JNS19405. [Epub ahead of print] PubMed PMID: 31419795.
3)

Huuska N, Netti E, Lehti S, Kovanen PT, Niemelä M, Tulamo R. Lymphatic vessels are present in human saccular intracranial aneurysms. Acta Neuropathol Commun. 2022 Sep 5;10(1):130. doi: 10.1186/s40478-022-01430-8. PMID: 36064651.
4)

Aoki T, Kataoka H, Morimoto M, Nozaki K, Hashimoto N. Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats. Stroke. 2007 Jan;38(1):162-9. Epub 2006 Nov 22. PubMed PMID: 17122420.
5)

Saini S, Speller-Brown B, Wyse E, Meier ER, Carpenter J, Fasano RM, Pearl MS. Unruptured Intracranial Aneurysms in Children With Sickle Cell Disease: Analysis of 18 Aneurysms in 5 Patients. Neurosurgery. 2015 Feb 12. [Epub ahead of print] PubMed PMID: 25710108.
6)

Pyysalo MJ, Pyysalo LM, Pessi T, Karhunen PJ, Lehtimäki T, Oksala N, Öhman JE. Bacterial DNA findings in ruptured and unruptured intracranial aneurysms. Acta Odontol Scand. 2016 May;74(4):315-20. doi: 10.3109/00016357.2015.1130854. Epub 2016 Jan 18. PubMed PMID: 26777430.
7)

Xu Z, Rui YN, Hagan JP, Kim DH. Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms. Neuromolecular Med. 2019 May 4. doi: 10.1007/s12017-019-08537-7. [Epub ahead of print] Review. PubMed PMID: 31055715.
8)

Rui YN, Xu Z, Fang X, Menezes MR, Balzeau J, Niu A, Hagan JP, Kim DH. The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent Focal Adhesion Assembly. Cell Physiol Biochem. 2017;43(6):2200-2211. doi: 10.1159/000484298. Epub 2017 Oct 25. PubMed PMID: 29069646.
9)

Santiago-Sim T, Fang X, Hennessy ML, Nalbach SV, DePalma SR, Lee MS, Greenway SC, McDonough B, Hergenroeder GW, Patek KJ, Colosimo SM, Qualmann KJ, Hagan JP, Milewicz DM, MacRae CA, Dymecki SM, Seidman CE, Seidman JG, Kim DH. THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Stroke. 2016 Dec;47(12):3005-3013. Epub 2016 Nov 15. Erratum in: Stroke. 2017 Aug;48(8):e240. PubMed PMID: 27895300; PubMed Central PMCID: PMC5134902.
10)

Zhang X, Wan Y, Feng J, Li M, Jiang Z. Involvement of TLR2/4‑MyD88‑NF‑κB signaling pathway in the pathogenesis of intracranial aneurysm. Mol Med Rep. 2021 Jan 26. doi: 10.3892/mmr.2021.11869. Epub ahead of print. PMID: 33655339.
11)

Qin K, Tian G, Zhou D, Chen G. Circular RNA circ-ARFIP2 regulates proliferation, migration and invasion in human vascular smooth muscle cells via miR-338-3p-dependent modulation of KDR. Metab Brain Dis. 2021 Apr 10. doi: 10.1007/s11011-021-00726-3. Epub ahead of print. PMID: 33837886.
12)

Zhang HF, Liang GB, Zhao MG, Zhao GF, Luo YH. Patients with intracranial aneurysms presented defects in regulatory T cells, which were associated with impairment in Tim-3 upregulation. Int Immunopharmacol. 2018 Sep 19;64:350-355. doi: 10.1016/j.intimp.2018.09.020. [Epub ahead of print] PubMed PMID: 30243071.

Intracranial aneurysm risk factors

Intracranial aneurysm risk factors

Observational evidence identified multiple clinical and anatomic risk factors for the formation of de novo IAs, including female sex, age <40 yr, family history, smoking history, multiple intracranial aneurysms at first diagnosis, and IC as the initial site. More aggressive long-term angiographic follow-up with digital subtraction angiography, computed tomography angiography, or magnetic resonance angiography is recommended for these patients 1).


Genetically determined HDL-C and LDL-C reduce the risk of intracranial aneurysm and ruptured intracranial aneurysm. The effects of different lipid-modifying drugs on IA need to be further investigated 2).


Although some previous reports have demonstrated an association between lipid accumulation and degenerative changes in aneurysm walls in humans, epidemiological studies have failed to identify dyslipidemia as a risk factor for intracranial aneurysm pathogenesis. Thus, Shimizu et al. examined whether an increase in serum cholesterol levels facilitates the progression of intracranial aneurysms in a rat model. Rats were given a high-fat diet (HFD) and subjected to an intracranial aneurysm model. The HFD elevated their serum cholesterol levels. The intracranial aneurysms induced at the anterior cerebral artery-olfactory artery bifurcation were significantly larger in the high-fat group than in the normal-chow group. Histological analysis demonstrated that the loss of medial smooth muscle layers was exacerbated in the high-fat group and indicated the presence of macrophage-derived foam cells in the lesions. In in vitro experiments, the expression levels of the pro-inflammatory genes induced by LPS in RAW264.7-derived foam cells were significantly higher than those in RAW264.7 cells. The combination of these results suggests that increased serum cholesterol levels facilitate degenerative changes in the media and the progression of intracranial aneurysms presumably through foam cell transformation 3).

Although several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture.

METHODS: Patients from the prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population.

RESULTS: The proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48).

CONCLUSIONS: Smoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification 4).

Intracranial aneurysms after radiotherapy (RT) have previously been reported. However, the majority of studies were case reports. Therefore, we performed a nationwide study to explore the risk of radiation-induced intracranial aneurysms.

METHODS: This study included patients diagnosed with head and neck cancer (ICD9: 140-149, 161). Intracranial aneurysms formation was identified using the following ICD9 codes: nonruptured cerebral aneurysm (ICD9:4373), aneurysm clipping (ICD9:3951). Patients who did not receive curative treatment and those with intracranial aneurysms before the diagnosis of head and neck cancer were excluded.

RESULTS: In total, 70,691 patients were included in the final analysis; they were categorized into the following three groups: nasopharyngeal carcinoma (NPC) with RT, non-NPC with RT, and non-NPC without RT. Patients in the NPC with RT group had the highest risk of developing intracranial aneurysms (hazard ratio (HR) 2.57; P <  0.001). In addition, hypertension was also a risk factor of developing intracranial aneurysms (HR 2.14; P <  0.01). The mean time interval from cancer diagnosis to intracranial aneurysm formation in the NPC with RT group was 4.3 ± 3.1 years.

CONCLUSIONS: Compared with the non-NPC with RT and the non-NPC without RT groups, patients with NPC who received RT had a higher risk of developing intracranial aneurysms 5).


1)

Hu S, Yu N, Li Y, Hao Z, Liu Z, Li MH. A Meta-Analysis of Risk Factors for the Formation of de novo Intracranial Aneurysms. Neurosurgery. 2019 Oct 1;85(4):454-465. doi: 10.1093/neuros/nyy332. PubMed PMID: 30085204.
2)

Zhang B, Dong S, Miao Y, Song G, Yuan F, Liu L, Xia S, Qin Y, Huo X, Wu Z, Miao Z, Mo D, Liu A; International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group. Effects of blood lipids and lipid-modifying drugs on intracranial aneurysms. Eur J Neurol. 2022 Jun 21. doi: 10.1111/ene.15471. Epub ahead of print. PMID: 35726534.
3)

Shimizu K, Miyata H, Abekura Y, Oka M, Kushamae M, Kawamata T, Mizutani T, Kataoka H, Nozaki K, Miyamoto S, Aoki T. High-Fat Diet Intake Promotes the Enlargement and Degenerative Changes in the Media of Intracranial Aneurysms in Rats. J Neuropathol Exp Neurol. 2019 Jul 24. pii: nlz057. doi: 10.1093/jnen/nlz057. [Epub ahead of print] PubMed PMID: 31340038.
4)

Schatlo B, Gautschi OP, Friedrich CM, Ebeling C, Jägersberg M, Kulscar Z, Pereira VM, Schaller K, Bijlenga P. Association of single and multiple aneurysms with tobacco abuse: an @neurIST risk analysis. Neurosurg Focus. 2019 Jul 1;47(1):E9. doi: 10.3171/2019.4.FOCUS19130. PubMed PMID: 31261132.
5)

Yang WH, Yang YH, Chen PC, Wang TC, Chen KJ, Cheng CY, Lai CH. Intracranial aneurysms formation after radiotherapy for head and neck cancer: a 10-year nationwide follow-up study. BMC Cancer. 2019 Jun 4;19(1):537. doi: 10.1186/s12885-019-5766-2. PubMed PMID: 31164088; PubMed Central PMCID: PMC6549276.

Intracranial dermoid cyst

Intracranial dermoid cyst

Intracranial dermoid cysts generally occur along the midline and are derived from the trapped somatic ectoderm during embryological development during third to fifth week of gestation.

The tumors typically arise in infants to young adults because of their congenital origin 1) 2) 3). Intracranial dermoid cyst are very rare, constituting less than 1% of intracranial tumor4), and are relatively rare in middle-aged or older people 5).

Many reports have mentioned the intradural posterior fossa and the midline as the preferential localization of these tumors 6) 7). In contrast, extradural dermoid cysts are a much rarer entity 8) 9).

see Parasellar dermoid cyst.

see Posterior fossa dermoid cyst.

see Asterional dermoid cyst.

Dermoid cysts are thought to occur as a developmental anomaly in which embryonic ectoderm is trapped in the closing neural tube between the 5th-6th weeks of gestation.

Dermoid cysts, like epidermoid cysts, are lined by stratified squamous epithelium. Unlike epidermoid cysts, however, they also have epidermal appendages such as hair follicles, sweat and sebaceous glands. The latter handles the secretion of sebum that imparts the characteristic appearance of these lesions on CT and MRI.

A common misconception is that dermoid cysts contain adipose tissue. This is not the case, as lipocytes are mesodermal in origin, and dermoid cysts (by definition) are purely ectodermal. A dermoid cyst with adipose tissue would be a teratoma.

Associated dermal sinuses cause earlier onset of clinical symptoms such as infection 10). Other common symptoms including headaches, seizures, and chemical meningitis, and visual disturbances occur late in the clinical course because of its slow-growing nature 11) 12) 13).

Many intracranial dermoid cysts are asymptomatic and only found incidentally. Often there is a long history of vague symptoms, with headache being a prominent feature

In case of rupture (spontaneous, traumatic, or iatrogenic (at resection)) leakage of sebum into the subarachnoid space results in an aseptic chemical meningitis.

The presentation is variable, ranging from a headache, to seizures, vasospasm and even death 14).

Occasionally, dermoid tumors are incidentally discovered on computed tomography (CT) of the brain or magnetic resonance imaging (MRI) following unrelated clinical complaints. They are also discovered during radiologic investigations of unexplained headaches, seizures, and rarely olfactory delusions.

On imaging, they are usually well-defined lobulated midline masses that have low attenuation (fat density) on CT and hypersignal on T1-weighted MRI images. Typically they do not enhance after contrast administration.

Although dermoid cysts are pathognomonic in appearance on a CT examination, the MRI is also of value in helping to understand the effect of extension and pressure of the mass. DWI is also important for support of the diagnosis and patient follow-up.

Radiograph

Historically, when skull x-rays were routinely used in the assessment of suspected intracranial pathology, a focal lucency due to the fatty sebum

CT

Typically dermoid cysts appear as well defined low attenuating (fat density) lobulated masses. Calcifications may be present in the wall. Enhancement is uncommon, and if present should at most be a thin peripheral rim.

Very rarely they demonstrate hyperdensity thought to be due to a combination of saponification, microcalcification and blood products. This is usually the case when present in the posterior fossa, although why this is the case is not certain.

MRI

Unlike intracranial lipomas that follow fat density on all sequences, intracranial dermoids have more variable signal characteristics:

T1 typically hyperintense (due to cholesterol components) droplets in the subarachnoid space may be visible if rupture has occurred

T1 C+ (Gd): generally do not enhance extensive pial enhancement may be present in chemical meningitis caused by ruptured cysts

T2: variable signal ranging from hypo to hyperintense.

  

Left parasellar extraaxial lesion 2.2 x 1.9 x 1.5 cm without evidence of contrast uptake.

Slight mass effect on the anterior aspect of the left temporal lobe.

Epidermoid cysts at one end (containing only desquamated squamous epithelium) and teratomas at the other (containing essentially any kind of tissue from all three embryonic tissue layers).

Intracranial lipoma: homogeneous fat attenuation/signal intensity, chemical shift artefact

Intracranial teratoma: immature, usually occur in the pineal region

Craniopharyngioma most are strikingly hyperintense on T2, most enhance strongly

Can be surgically excised and provided complete excision is achieved recurrence is uncommon. Sometimes due to local adhesion of the capsule to vital structures, incomplete excision must be performed. Recurrent growth, in either case, is slow 15).

Spontaneous rupture of dermoid tumor is a potentially serious complication that can lead to meningitis, seizures, cerebral ischemia and hydrocephalus.

Rupture of these benign lesions occurs in only a small percentage of patients, and usually occurs spontaneously 16) 17)

Traumatic rupture of an intracranial dermoid cyst is an exceedingly rare event, with only three cases reported in the literature to date 18) 19) 20).

Extremely rare malignant transformation into squamous cell carcinoma has been reported 21).

Intracranial dermoid cyst case reports.


1) , 11)

Akdemir G, Dağlioğlu E, Ergüngör M F. Dermoid lesion of the cavernous sinus: case report and review of the literature. Neurosurg Rev. 2004;27:294–298.
2) , 12)

Lunardi P, Missori P. Supratentorial dermoid cysts. J Neurosurg. 1991;75:262–266.
3) , 10)

Caldarelli M Massimi L Kondageski C Di Rocco C Intracranial midline dermoid and epidermoid cysts in children J Neurosurg 2004100(5 Suppl Pediatrics):473–480.480
4) , 6)

Guidetti B, Gagliardi F M. Epidermoid and dermoid cysts. Clinical evaluation and late surgical results. J Neurosurg. 1977;47:12–18.
5) , 8)

Ammirati M, Delgado M, Slone H W, Ray-Chaudhury A. Extradural dermoid tumor of the petrous apex. Case report. J Neurosurg. 2007;107:426–429.
7)

Bogdanowicz W M, Wilson D H. Dermoid cyst of the fourth ventricle demonstrated on brain scan. Case report. J Neurosurg. 1972;36:228–230.
9)

Blythe J N, Revington P J, Nelson R. Anterior cranial fossa dermoid cyst: case report. Br J Oral Maxillofac Surg. 2007;45:661–663.
13)

Rubin G, Scienza R, Pasqualin A, Rosta L, Da Pian R. Craniocerebral epidermoids and dermoids. A review of 44 cases. Acta Neurochir (Wien) 1989;97:1–16.
14)

Brown JY, Morokoff AP, Mitchell PJ, Gonzales MF. Unusual imaging appearance of an intracranial dermoid cyst. AJNR Am J Neuroradiol. 2001 Nov-Dec;22(10):1970-2. PubMed PMID: 11733334.
15)

Yaşargil MG. Microneurosurgery IV/B, Microsurgery of CNS Tumors. (1996) ISBN:3131165014
16)

El-Bahy K, Kotb A, Galal A, El-Hakim A. Ruptured intracranial dermoid cysts. Acta Neurochir (Wien) 2006;148:457–62.
17)

Stendel R, Pietila TA, Lehmann K, Kurth R, Suess O, Brock M. Ruptured intracranial dermoid cysts. Surg Neurol. 2002;57:391–8.
18)

Kim IY, Jung S, Jung TY, Kang SS, Kim TS. Traumatic rupture of an intracranial dermoid cyst. J Clin Neurosci. 2008;15:469–71.
19)

Park SK, Cho KG. Recurrent intracranial dermoid cyst after subtotal removal of traumatic rupture. Clin Neurol Neurosurg. 2012;114:421–4.
20)

Phillips WE, 2nd, Martinez CR, Cahill DW. Ruptured intracranial dermoid tumor secondary to closed head trauma. Computed tomography and magnetic resonance imaging. J Neuroimaging. 1994;4:169–70
21)

Osborn AG, Preece MT. Intracranial cysts: radiologic-pathologic correlation and imaging approach. Radiology. 2006 Jun;239(3):650-64. Review. PubMed PMID: 16714456.

Unruptured intracranial aneurysm treatment score

Unruptured intracranial aneurysm treatment score

see also PHASES score.

The unruptured intracranial aneurysm treatment score (UIATS) was published in April 2015 as a multidisciplinary consensus regarding the treatment of unruptured intracranial aneurysms (UIA).

Etminan et al. endeavored to develop an unruptured intracranial aneurysm treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in Unruptured intracranial aneurysm (UIA) management and research.

An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39-panel members involved in the identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr) (vr = 0 indicating excellent agreement and vr* = 1 indicating poor agreement).

The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033).

This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA 1)   


The Unruptured Intracranial Aneurysm Treatment Score (UIATS) offers support for clinical decision making and has been shown to correlate with real-life decisions in clinical practice. However, there is no data concerning the correlation of patient Unruptured intracranial aneurysm outcome and UIATS. Patients presenting to the Department of Neurosurgery,University Hospital Leipzig, outpatient clinic between January 1st, 2014, and December 31st, 2017 were retrospectively analyzed. They recorded the Extended Glasgow Outcome Scale (GOS-E) for the longest possible follow-up, the choice of treatment, complications, and UIATS recommendation. They included 221 patients with 322 UIA. 124 (38.5 %) UIA were observed and 198 (61.5 %) were occluded, of which 62 (31.3 %) underwent open surgery and 136 (68.7 %) were treated endovascularly. Spearman’s rank correlation between the treatment choice and conclusive UIATS recommendation was 0.362 (p < 0.001). If UIATS was inconclusive, there were significantly more treatment-associated deteriorations (10/66 versus 7/132, p = 0.020). Otherwise, UIATS was not significantly associated with outcome. Therefore, the treatment choice for UIA remains an individual decision. However, inconclusive UIATS must trigger vigilance and may be a negative prognostic marker for complications 2).


A tertiary center with focus on vascular neurosurgery, aimed to investigate whether there treatment decision-making in patients with UIA has been in accordance with the published UIATS. A retrospective analysis of patients admitted to the center with UIA was performed. UIATS was applied to all identified UIA. Three decision groups were defined: (a) UIATS favoring treatment, (b) UIATS favoring observation, and © UIATS inconclusive. These results were then compared to our clinical decisions. Spearman’s rank-order correlation (ρ) was run to determine the relationship between the UIATS and our clinical decisions. Cases of discrepancies between UIATS and our clinical decisions were then examined for complications, defined as periprocedural adverse events in treated aneurysms, or aneurysm rupture in untreated aneurysms. Ninety-three patients with 147 UIA were included. A total of 118/147 (80.3%) UIA were treated. In 70/118 (59.3%), UIATS favored treatment, in 18/118 (15.3%), it was inconclusive, and in 30/118 (25.4%), it favored observation. A total of 29/147 (19.7%) UIA were not treated. In 15/29 (51.7%), UIATS favored observation, in 9/29 (31%), it favored treatment, and in 5/29 (17.2%), it was inconclusive (ρ = 0.366, p < 0.01). Discrepancies between UIATS and our clinical decisions did not correlate with complications (ρ = 0.034, p = 0.714). Our analysis shows that our more intuitive clinical decision-making has been in line with UIATS. Our treatment decisions did not correlate with an increased rate of complications 3).


The purpose of the study of Ravindra et al. was to compare the unruptured intracranial aneurysm treatment score (UIATS) recommendations with the real-world experience in a quaternary academic medical center with a high volume of patients with unruptured intracranial aneurysms (UIAs).

All patients with UIAs evaluated during a 3-year period were included. All factors included in the UIATS were abstracted, and patients were scored using the UIATS. Patients were categorized in a contingency table assessing UIATS recommendation versus real-world treatment decision. The authors calculated the percentage of misclassification, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. RESULTS A total of 221 consecutive patients with UIAs met the inclusion criteria: 69 (31%) patients underwent treatment and 152 (69%) did not. Fifty-nine (27%) patients had a UIATS between -2 and 2, which does not offer a treatment recommendation, leaving 162 (73%) patients with a UIATS treatment recommendation. The UIATS was significantly associated with treatment (p < 0.001); however, the sensitivity, specificity, and percentage of misclassification were 49%, 80%, and 28%, respectively. Notably, 51% of patients for whom treatment would be recommended by the UIATS did not undergo treatment in the real-world cohort and 20% of patients for whom conservative management would be recommended by UIATS had intervention. The area under the ROC curve was 0.646.

Compared with the authors’ experience, the UIATS recommended overtreatment of UIAs. Although the UIATS could be used as a screening tool, individualized treatment recommendations based on consultation with a cerebrovascular specialist are necessary. Further validation with longitudinal data on rupture rates of UIAs is needed before widespread use 4).


1)

Etminan N, Brown RD Jr, Beseoglu K, Juvela S, Raymond J, Morita A, Torner JC, Derdeyn CP, Raabe A, Mocco J, Korja M, Abdulazim A, Amin-Hanjani S, Al-Shahi Salman R, Barrow DL, Bederson J, Bonafe A, Dumont AS, Fiorella DJ, Gruber A, Hankey GJ, Hasan DM, Hoh BL, Jabbour P, Kasuya H, Kelly ME, Kirkpatrick PJ, Knuckey N, Koivisto T, Krings T, Lawton MT, Marotta TR, Mayer SA, Mee E, Pereira VM, Molyneux A, Morgan MK, Mori K, Murayama Y, Nagahiro S, Nakayama N, Niemelä M, Ogilvy CS, Pierot L, Rabinstein AA, Roos YB, Rinne J, Rosenwasser RH, Ronkainen A, Schaller K, Seifert V, Solomon RA, Spears J, Steiger HJ, Vergouwen MD, Wanke I, Wermer MJ, Wong GK, Wong JH, Zipfel GJ, Connolly ES Jr, Steinmetz H, Lanzino G, Pasqualin A, Rüfenacht D, Vajkoczy P, McDougall C, Hänggi D, LeRoux P, Rinkel GJ, Macdonald RL. The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus. Neurology. 2015 Sep 8;85(10):881-9. doi: 10.1212/WNL.0000000000001891. Epub 2015 Aug 14. PubMed PMID: 26276380; PubMed Central PMCID: PMC4560059.
2)

Wende T, Kasper J, Wilhemy F, Prasse G, Quäschling U, Haase A, Meixensberger J, Nestler U. Comparison of the unruptured intracranial aneurysm treatment score recommendations with clinical treatment results – A series of 322 aneurysms. J Clin Neurosci. 2022 Feb 9;98:104-108. doi: 10.1016/j.jocn.2022.01.038. Epub ahead of print. PMID: 35151060.
3)

Hernández-Durán S, Mielke D, Rohde V, Malinova V. The application of the unruptured intracranial aneurysm treatment score: a retrospective, single-center study. Neurosurg Rev. 2018 Feb 1. doi: 10.1007/s10143-018-0944-2. [Epub ahead of print] PubMed PMID: 29388120.
4)

Ravindra VM, de Havenon A, Gooldy TC, Scoville J, Guan J, Couldwell WT, Taussky P, MacDonald JD, Schmidt RH, Park MS. Validation of the unruptured intracranial aneurysm treatment score: comparison with real-world cerebrovascular practice. J Neurosurg. 2017 Oct 6:1-7. doi: 10.3171/2017.4.JNS17548. [Epub ahead of print] PubMed PMID: 28984518.

Intracranial aneurysm clipping

Intracranial aneurysm clipping

Evolution in the surgical treatment of intracranial aneurysms is driven by the need to refine and innovate. From an early application of the Hunterian carotid ligation to modern-day sophisticated aneurysm clip designs, progress was made through dedication and technical maturation of the cerebrovascular neurosurgeons to overcome challenges in their practices. The global expansion of endovascular services has challenged the existence of aneurysm surgery, changing the complexity of aneurysm case mix and volume that are presently referred for surgical repair. Concepts of how to best treat intracranial aneurysms have evolved over generations, and will continue to do so with further technological innovations. As with the evolution of any type of surgery, innovations frequently arise from the criticism of currently available techniques 1).


Intracranial Aneurysm treatment with surgery remains the recommended form of treatment in high-grade SAH patients with intracerebral space occupying hematomas, where the surgical decompression of the mass effect may be warranted, and along with it the clipping of the bleeding aneurysm.

Less invasive surgical approaches for intracranial aneurysm clipping may reduce length of hospital stay, surgical morbidity, treatment cost, and improve patient outcomes.

In the US, a number of training programs are including endovascular exposure to residents during their training, assuming the endovascular suite as a regular OR room.

The training of surgeons in both techniques seems promising and the right way to go, regardless of whether a dually trained neurosurgeon will end up opting for the use of one technique over the other. The important is that we guarantee the ability to deliver our patients the best possible care by providing them with a choice that is not born out of a turf war but based on evidence both on a general, but similarly important, local one 2).

Time from rupture to treatment is a crucial factor in determining outcome.

Practice of delayed surgery to avoid edematous brain has been replaced by early surgery to minimize risk from rebleeding and vasospasm. Mahaney et al. in their analysis of intraoperative hypothermia for aneurysm surgery trial (IHAST) data observed that patients operated early (day 0-2) or late (day 7-14) fared significantly better than those operated during intermediate phase (day 3-6). Change in surgical strategy has posed challenge to the anesthesiologists as increasing number of patients are operated during off-work hours in inadequately optimized state with less expert help.


Nieuwkamp et al., performed a retrospective observational study on the timing of intracranial aneurysm surgery in The Netherlands over a two-year period.

In eight hospitals they identified 1,500 patients with an aneurysmal subarachnoid hemorrhage. They were subjected to predefined inclusion criteria. They included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage.

They included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT

Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition.

In this observational study they found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling 3).

The guidelines relevant to the anesthesiologists in the day-to-day perioperative management of patients with ruptured intracranial aneurysm given by various societies are:

Diringer MN, Bleck TP, Claude Hemphill J, 3rd, Menon D, Shutter L, Vespa P, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: Recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15:211–40.

Bederson JB, Connolly ES, Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40:994–1025.

Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G, et al. European Stroke Organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis. 2013;35:93–112.


Both intravenous and inhalational anesthetic technique may be used for maintenance keeping in mind the objectives of stable intraoperative hemodynamics, early smooth recovery and effect on special monitoring techniques. Cerebral perfusion increases with isoflurane when compared with propofol without increase in ICP in aSAH.

Hypocapnia is not essential in good grade patients as it can reduce ICP and increase transmural pressure within aneurysmal sac predisposing it to rupture. In poor grade patients, hyperventilation however is beneficial to reduce ICP and provide lax brain.

Brain laxity is crucial to obtain good surgical access to the aneurysm without causing IOAR or compromising underlying brain from excessive retractor pressure. This is important as early surgery risks a tense/full brain and dissection without adequate exposure can result in IOAR. Both 20% mannitol and 3% hypertonic saline are suitable osmotic agents for intraoperative brain relaxation in the dose of 2-4 ml/kg. Head end elevation, avoiding jugular venous compression, avoiding high concentration of inhalational agents and nitrous-oxide and mild hyperventilation are other measures to achieve a lax brain. If full brain persists, additional measures like moderate hyperventilation, switching to intravenous anesthetic maintenance and release of cerebrospinal fluid might be helpful. 4).

Intracranial aneurysm surgery by clipping requires meticulous technique and is usually performed through open approaches. Endoscopic endonasal clipping of intracranial aneurysms may use the same techniques through an alternative corridor.

To enhance visual confirmation of regional anatomy, endoscopy was introduced.

see Endoscopic endonasal approach for intracranial aneurysm

see Surgical clipping versus endovascular coiling for intracranial aneurysm

Clipping is an important technique for intracranial aneurysm surgery. Although clip mechanisms and features have been refined, little attention has been paid to clip appliers. Clip closure is traditionally achieved by opening the grip of the clip applier. Sato et al.. reconsidered this motion and identified an important drawback, namely that the standard applier holding power decreased at the moment of clip release, which could lead to unstable clip application develop a forceps to address this clip applier design flaw.The new clip applier has a non–cross-type fulcrum that is closed at the time of clip release, with an action similar to that of a bipolar forceps or scissors. Thus, a surgeon can steadily apply the clip from various angles. They successfully used the clip applier to treat 103 aneurysms. Although training was required to ensure smooth applier use, no difficulties associated with applier use were noted. This clip applier can improve clipping surgery safety because it offers additional stability during clip release. 5).

Pterional approach via standard frontotemporal craniotomy and interhemispheric approach via bifrontal craniotomy is the gold standard for clipping of cerebral aneurysms in the anterior circulationEndovascular treatment is now widely used, but subsets of aneurysms are still indicated for surgical clipping. Modern technological advances allow less invasive clipping techniques such as the keyhole approach. Mori and Watanabe discussed the surgical indications, preoperative simulation, surgical techniques, and pros and cons of keyhole (supraorbital) clipping. Selection of standard craniotomy or keyhole craniotomy should be uncontroversial, but keyhole clipping requires definite surgical indications based on the characteristics of the target aneurysm for safe clipping 6).

see Intracranial aneurysm clipping complications.

A challenge is to ensure noninclusion of normal vessel/perforators within the clip and perform complete aneurysmal isolation. This is done with either intraoperative microvascular Doppler sonography (IMD) or Indocyanine green videoangiography (ICG-VA) as they are simple and safe. Anesthesiologists administer ICG and also help perform IMD. ICG-VA appropriately assessed vessel patency and aneurysm obliteration in 93.5% of 109 aneurysms clipped 7) However, ICG can cause transient oxygen desaturation 8). IMD use confirms aneurysm isolation and patency of parent vessel and branching arteries. Hui et al. observed that clip repositioning was required based on IMD findings in 24% of aneurysms clipped in 91 patients and concluded that IMD could reduce the rate of residual aneurysm and unanticipated vessel stenosis 9).

The complete clipping of a cerebral aneurysm usually warrants its sustained occlusion, while clip remnants may have far-reaching consequences. The aim of this study is to identify the risk factors for clip remnants requiring retreatment and/or exhibiting growth. METHODS All consecutive patients with primary aneurysm clipping performed at University Hospital of Essen between January 1, 2003, and December 31, 2013, were eligible for this study. Aneurysm occlusion was judged on obligatory postoperative digital subtraction angiography and the need for repeated vascular control. The identified clip remnants were correlated with various demographic and clinical characteristics of the patients, aneurysm features, and surgery-related aspects. RESULTS Of 616 primarily clipped aneurysms, postoperative angiography revealed 112 aneurysms (18%) with clip remnants requiring further control (n = 91) or direct retreatment (n = 21). Seven remnants exhibited growth during follow-up, whereas 2 cases were associated with aneurysmal bleeding. Therefore, a total of 28 aneurysms (4.5%) were retreated as clip remnants (range 1 day to 67 months after clipping). In the multivariate analysis, the need for retreatment of clip remnant was correlated with the aneurysm’s initial size (> 12 mm; OR 3.22; p = 0.035) and location (anterior cerebral artery > internal carotid artery > posterior circulation > middle cerebral artery; OR 1.85; p = 0.003). Younger age with a cutoff at 45 years (OR 33.31; p = 0.004) was the only independent predictor for remnant growth. CONCLUSIONS The size and location of the aneurysm are the main risk factors for clip remnants requiring retreatment. Because of the risk for growth, younger individuals (< 45 years old) with clip remnants require a long-term (> 5 years) vascular follow-up. Clinical trial registration no: DRKS00008749 (Deutsches Register Klinischer Studien) 10).

Total index hospitalization costs for clipping are lower than for coiling. Costs of clipping and coiling are driven by different clinical variables. The cost of coils and devices is the predominant contributor to the higher total costs of coiling 11).

The mechanisms underlying neurocognitive changes after surgical clipping of unruptured intracranial aneurysms (UIAs) are poorly understood.

Minimal structural damage visualized on T2-weighted images at 6 months as a result of factors such as pial/microvascular injury and excessive retraction during surgical manipulation could cause subtle but significant negative effects on postoperative neurocognitive function after surgical clipping of a UIA. However, this detrimental effect was small, and based on the group-rate analysis

Successful and meticulous surgical clipping of a UIA does not adversely affect postoperative cognitive function 12).

Results of treatment after clipping and coiling do not differ in total for all patients, but differ depending on the presence of bleeding. Patients with bleeding aneurysms achieve better outcomes after coiling, and patients with non-bleeding aneurysms achieve better outcomes after clipping 13).

Risk of ischemia during intracranial aneurysm surgery is significantly related to temporary clipping time and final clipping that might incorporate a perforator.

Abdulrauf et al. attempted to assess the potential added benefit to patient outcomes of “awake” neurological testing when compared with standard neurophysiological testing performed under general anesthesia. The procedure is performed after the induction of conscious sedation, and for the neurological testing, the patient is fully awake.

They conducted an institutional review board-approved prospective study of clipping unruptured intracranial aneurysms (UIAs) in 30 consecutive adult patients who underwent awake clipping. The end points were the incidence of stroke/cerebrovascular accident (CVA), death, discharge to a long-term facility, length of stay, and 30-day modified Rankin Scale score. All clinical and neurophysiological intraoperative monitoring data were recorded.

The median patient age was 52 years (range 27-63 years); 19 (63%) female and 11 (37%) male patients were included. Twenty-seven (90%) aneurysms were anterior, and 3 (10%) were posterior circulation aneurysms. Five (17%) had been coiled previously, 3 (10%) had been clipped previously, 2 (7%) were partially calcified, and 2 (7%) were fusiform aneurysms. Three patients developed synchronous clinical neurological and neurophysiological changes during temporary clipping with consequent removal of the temporary clip and reversal of those clinical and neurophysiological changes. Three patients developed asynchronous clinical neurological and neurophysiological changes. These 3 patients developed hemiparesis without changes in neurophysiological monitoring results. One patient developed linked clinical neurological and neurophysiological changes during final clipping that were not reversed by reapplication of the clip, and the patient had a CVA. Four patients with internal carotid artery ophthalmic segment aneurysms underwent visual testing with final clipping, and 1 of these patients required repositioning of the clip. Three patients who required permanent occlusion of a vessel as part of their aneurysm treatment underwent a 10-minute intraoperative clinical respective-vessel test occlusion. The median length of stay was 3 days (range 1-5 days). The median modified Rankin Scale score was 1 (range 0-3). All of the patients were discharged to home from the hospital except for 1 who developed a CVA and was discharged to a rehabilitation facility. There were no deaths in this series.

The 3 patients who developed neurological deterioration without a concomitant neurophysiological finding during temporary clipping revealed a potential advantage of awake aneurysm surgery (i.e., in decreasing the risk of ischemic injury) 14).

see Virtual reality simulator for aneurysmal clipping surgery.

A total of 53 patients from Phoenix and San Francisco, who initially presented with a subarachnoid hemorrhage and underwent surgical clipping of a previously coiled intracranial aneurysm between December 1997 and December 2014 were studied. Clinical features, hospital course, and preoperative and most recent functional status (Glasgow Outcome Scale score) were reviewed retrospectively.

The mean time interval from coiling to clipping was 2.6 years, and mean follow-up was 5.5 years (range, 0.1-14.7 years). Five patients (9.8%) presented with rebleed prior to clipping. Most patients (79.3%, 42/53) experienced good neurologic outcomes. Most showed no change (81%, 43/53) or improvement (13%, 7/53) in functional status after microsurgical clipping. One patient (2%) deteriorated clinically, and there were 2 mortalities (4%).

Microsurgical clipping of previously ruptured, coiled aneurysms is a promising treatment method with favorable clinical outcomes 15).


Retrospective review of the medical records of 320 patients with 416 aneurysms treated with microsurgical clipping from 2008 to 2016 in a single neurosurgical center in Brazil. This study evaluated postoperative outcome, using the modified Rankin Scale (mRS) on hospital discharge, treatment efficacy, assessed by digital subtraction angiography (DSA) performed postoperatively, and mortality.

Among 320 patients with aneurysms, 228 patients presented with ruptured aneurysms and 92 patients with unruptured aneurysms. Overall, 81 (26,3%) presented poor outcome (mRs>2) while 227 (73,4%) showed good outcome. The presence of a ruptured aneurysm was a statistically significant factor for poor outcome (p<0,001) and mortality (p<0,015). Giant and large aneurysms were also associated with poor outcome (p=0,004). When we analyze separately, unruptured aneurysms with poor outcome were only associated with aneurysms size. Among the patients with ruptured aneurysms, those with Hunt Hess (HH) > 2 on hospital admission showed unfavorable outcomes (p<0,0001). Among patients submitted to postoperative DSA, 207 (89,8%) had complete occlusion of the aneurysms and 24 (10,2%) presented residual aneurysms, with reoperation required in eight cases.

Microsurgical treatment of intracranial aneurysms is an effective and safe method 16).


1)

Lai LT, O’Neill AH. History, Evolution and Continuing Innovations of Intracranial Aneurysm Surgery. World Neurosurg. 2017 Feb 9. pii: S1878-8750(17)30166-3. doi: 10.1016/j.wneu.2017.02.006. [Epub ahead of print] Review. PubMed PMID: 28189863.
2)

Santiago BM, Cunha E Sá M. How do we maintain competence in aneurysm surgery. Acta Neurochir (Wien). 2015 Jan;157(1):9-11. doi: 10.1007/s00701-014-2265-8. Epub 2014 Nov 14. PubMed PMID: 25391972.
3)

Nieuwkamp DJ, de Gans K, Algra A, Albrecht KW, Boomstra S, Brouwers PJ, Groen RJ, Metzemaekers JD, Nijssen PC, Roos YB, Tulleken CA, Vandertop WP, van Gijn J, Vos PE, Rinkel GJ. Timing of aneurysm surgery in subarachnoid haemorrhage–an observational study in The Netherlands. Acta Neurochir (Wien). 2005 Aug;147(8):815-21. PubMed PMID: 15944811.
4)

Sriganesh K, Venkataramaiah S. Concerns and challenges during anesthetic management of aneurysmal subarachnoid hemorrhage. Saudi J Anaesth. 2015 Jul-Sep;9(3):306-13. doi: 10.4103/1658-354X.154733. Review. PubMed PMID: 26240552; PubMed Central PMCID: PMC4478826.
5)

Sato A, Koyama JI, Hanaoka Y, Hongo K. A Reverse-Action Clip Applier for Aneurysm Surgery. Neurosurgery. 2015 Mar 12. [Epub ahead of print] PubMed PMID: 25774701.
6)

Mori K, Watanabe S. Keyhole Approach in Cerebral Aneurysm Surgeries. Adv Tech Stand Neurosurg. 2022;44:265-275. doi: 10.1007/978-3-030-87649-4_15. PMID: 35107685.
7)

Özgiray E, Aktüre E, Patel N, Baggott C, Bozkurt M, Niemann D, et al. How reliable and accurate is indocyanine green video angiography in the evaluation of aneurysm obliteration? Clin Neurol Neurosurg. 2013;115:870–8.
8)

Sriganesh K, Vinay B, Bhadrinarayan V. Indocyanine green dye administration can cause oxygen desaturation. J Clin Monit Comput. 2013;27:371.
9)

Hui PJ, Yan YH, Zhang SM, Wang Z, Yu ZQ, Zhou YX, et al. Intraoperative microvascular Doppler monitoring in intracranial aneurysm surgery. Chin Med J (Engl) 2013;126:2424–9.
10)

Jabbarli R, Pierscianek D, Wrede K, Dammann P, Schlamann M, Forsting M, Müller O, Sure U. Aneurysm remnant after clipping: the risks and consequences. J Neurosurg. 2016 Feb 12:1-7. [Epub ahead of print] PubMed PMID: 26871206.
11)

Duan Y, Blackham K, Nelson J, Selman W, Bambakidis N. Analysis of short-term total hospital costs and current primary cost drivers of coiling versus clipping for unruptured intracranial aneurysms. J Neurointerv Surg. 2014 Jun 2. pii: neurintsurg-2014-011249. doi: 10.1136/neurintsurg-2014-011249. [Epub ahead of print] PubMed PMID: 24891453.
12)

Inoue T, Ohwaki K, Tamura A, Tsutsumi K, Saito I, Saito N. Subtle structural change demonstrated on T2-weighted images after clipping of unruptured intracranial aneurysm: negative effects on cognitive performance. J Neurosurg. 2014 Jan 31. [Epub ahead of print] PubMed PMID: 24484231.
13)

Birski M, Wałęsa C, Gaca W, Paczkowski D, Birska J, Harat A. Clipping versus coiling for intracranial aneurysms. Neurol Neurochir Pol. 2014 Mar-Apr;48(2):122-9. doi: 10.1016/j.pjnns.2014.03.002. Epub 2014 Mar 31. PubMed PMID: 24821638.
14)

Abdulrauf SI, Vuong P, Patel R, Sampath R, Ashour AM, Germany LM, Lebovitz J, Brunson C, Nijjar Y, Kyle Dryden J, Khan MQ, Stefan MG, Wiley E, Cleary RT, Reis C, Walsh J, Buchanan P. “Awake” clipping of cerebral aneurysms: report of initial series. J Neurosurg. 2016 Oct 21:1-8. [Epub ahead of print] PubMed PMID: 27767401.
15)

Nisson PL, Meybodi AT, Roussas A, James W, Berger GK, Benet A, Lawton MT. Surgical Clipping of Previously Ruptured, Coiled Aneurysms: Outcome Assessment in 53 Patients. World Neurosurg. 2018 Dec;120:e203-e211. doi: 10.1016/j.wneu.2018.07.293. Epub 2018 Aug 23. PubMed PMID: 30144619.
16)

Dellaretti M, Ronconi D, Batista DM, de Souza RF, de Almeida CER, Fontoura RR, Botelho Antunes PR, Quadros RS. Safety and Efficacy of Surgical Treatment of Intracranial Aneurysms: The Experience of a Single Brazilian Center. World Neurosurg. 2018 Jun 20. pii: S1878-8750(18)31307-X. doi: 10.1016/j.wneu.2018.06.091. [Epub ahead of print] PubMed PMID: 29935315.