Category Archives: Articles

Update: Unruptured intracranial aneurysm treatment score

Unruptured intracranial aneurysm treatment score

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 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 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 2).

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)

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.

Update: Spontaneous intracerebral hemorrhage expansion

Spontaneous intracerebral hemorrhage expansion

Spontaneous intracerebral hemorrhage expansion occurs in about 30% of patients and is related to poor outcome 1).

Patient with prior Warfarin use and intraventricular hemorrhage (IVH) are at risk of hematoma expansion. Aggressive measures to prevent hematoma growth are important in these patients 2).

Hematoma volume HV>16, hematoma heterogeneity HH, 1.5 h-systolic BP SBP>160) can be a practical tool for prediction of ICH growth in the acute stage. Further prospective studies are warranted to validate the ability of this model to predict clinical outcome 3).

Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign 4).

Large ICHs were significantly more irregular in shape, heterogeneous in density, and had greater growth. Density heterogeneity independently predicted ICH growth using some definitions 5).

The inconsistency in findings may be caused by ambiguous definition of irregular shape.


Very small hematomas are unlikely to expand and have a low spot sign prevalence. Hemostatic therapy trials may be best targeted at hemorrhages >3 mL in volume 6).

Compared with previously reported predictors for hematoma expansion on non-enhanced CT, such as blend signblack hole sign and heterogeneous density, CTA spot sign has better predictive accuracy for hematoma expansion 7) 8) 9).

However, CTA is not available to all medical centers, especially in some remote areas and non-enhanced CT is sometimes the only emergency neuroimaging examination for spontaneous ICH patients. Thus, it is still important to investigate predictors for hematoma expansion on non-enhanced CT.


A non-enhanced computed tomography (CT) based finding, termed the ‘satellite sign‘, was reported to be a novel predictor for poor outcome in spontaneous ICH. However, it is still unclear whether the presence of the satellite sign is related to hematoma expansion.

Initial computed tomography angiography (CTA) was conducted within 6h after ictus. Satellite sign on non-enhanced CT and spot sign on CTA were detected by two independent reviewers. The sensitivity and specificity of both satellite sign and spot sign were calculated. Receiver-operator analysis was conducted to evaluate their predictive accuracy for hematoma expansion.

This study included 153 patients. Satellite sign was detected in 58 (37.91%) patients and spot sign was detected in 38 (24.84%) patients. Among 37 patients with hematoma expansion, 22 (59.46%) had satellite sign and 23 (62.16%) had spot sign. The sensitivity and specificity of satellite sign for prediction of hematoma expansion were 59.46% and 68.97%, respectively. The sensitivity and specificity of spot sign were 62.16% and 87.07%, respectively. The area under the curve (AUC) of satellite sign was 0.642 and the AUC of spot sign was 0.746. (P=0.157)

The results suggest that the satellite sign is an independent predictor for hematoma expansion in spontaneous ICH. Although spot sign has the higher predictive accuracy, satellite sign is still an acceptable predictor for hematoma expansion when CTA is unavailable

Yu et al. compared the predictive values of spot sign and satellite sign for hematoma expansion. Compared with satellite sign, spot sign had higher sensitivity and specificity. In addition, spot sign had a larger AUC than satellite sign, but no significant difference existed. Thus, CTA spot sign seems to be a better predictor for hematoma expansion in spontaneous ICH patients, but satellite sign is still an acceptable predictor for hematoma expansion when CTA is unavailable.

The study has several limitations. First, this was a retrospective study with limited sample size in a single medical center. Second, the association between satellite sign and prognosis was not investigated because of insufficient follow-up data. Furthermore, the onset-to-CTA time was relatively long, which could influence the predictive accuracy of both spot sign and satellite sign.

In conclusion, the study demonstrated that the satellite sign was an independent predictor for hematoma expansion in spontaneous ICH patients. Spot sign has higher accuracy for predicting hematoma expansion, but the satellite sign is still an acceptable predictor when CTA is unavailable. Further multi-center, prospective studies with larger sample sizes are still needed to confirm the utility and validity of the satellite sign in predicting hematoma expansion in spontaneous ICH patients 10).

1)

H.B. Brouwers, Y. Chang, G.J. Falcone, X. Cai, A.M. Ayres, T.W. Battey, A. Vashkevich, K.A. McNamara, V. Valant, K. Schwab, S.C. Orzell, L.M. Bresette, S.K. Feske, N.S. Rost, J.M. Romero, A. Viswanathan, S.H. Chou, S.M. Greenberg, J. Rosand, J.N. Goldstein, Predicting hematoma expansion after primary intracerebral hemorrhage, JAMA Neurol. 1 (2) (2014) 158–164.
2)

Yaghi S, Dibu J, Achi E, Patel A, Samant R, Hinduja A. Hematoma expansion in spontaneous intracerebral hemorrhage: predictors and outcome. Int J Neurosci. 2014 Dec;124(12):890-3. doi: 10.3109/00207454.2014.887716. Epub 2014 Feb 28. PubMed PMID: 24472073.
3)

Takeda R, Ogura T, Ooigawa H, Fushihara G, Yoshikawa S, Okada D, Araki R, Kurita H. A practical prediction model for early hematoma expansion in spontaneous deep ganglionic intracerebral hemorrhage. Clin Neurol Neurosurg. 2013 Jul;115(7):1028-31. doi: 10.1016/j.clineuro.2012.10.016. Epub 2012 Dec 14. PubMed PMID: 23245855.
4) , 7)

Blacquiere D, Demchuk AM, Al-Hazzaa M, Deshpande A, Petrcich W, Aviv RI, Rodriguez-Luna D, Molina CA, Silva Blas Y, Dzialowski I, Czlonkowska A, Boulanger JM, Lum C, Gubitz G, Padma V, Roy J, Kase CS, Bhatia R, Hill MD, Dowlatshahi D; PREDICT/Sunnybrook ICH CTA Study Group. Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant Hematoma Expansion. Stroke. 2015 Nov;46(11):3111-6. doi: 10.1161/STROKEAHA.115.010566. Epub 2015 Oct 8. PubMed PMID: 26451019.
5)

Barras CD, Tress BM, Christensen S, MacGregor L, Collins M, Desmond PM, Skolnick BE, Mayer SA, Broderick JP, Diringer MN, Steiner T, Davis SM; Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Density and shape as CT predictors of intracerebral hemorrhage growth. Stroke. 2009 Apr;40(4):1325-31. doi: 10.1161/STROKEAHA.108.536888. Epub 2009 Mar 12. PubMed PMID: 19286590.
6)

Dowlatshahi D, Yogendrakumar V, Aviv RI, Rodriguez-Luna D, Molina CA, Silva Y, Dzialowski I, Czlonkowska A, Boulanger JM, Lum C, Gubitz G, Padma V, Roy J, Kase CS, Bhatia R, Hill MD, Demchuk AM; PREDICT/Sunnybrook ICH CTA study group. Small intracerebral hemorrhages have a low spot sign prevalence and are less likely to expand. Int J Stroke. 2016 Feb;11(2):191-7. doi: 10.1177/1747493015616635. PubMed PMID: 26783310.
8)

Zheng J, Yu Z, Xu Z, Li M, Wang X, Lin S, Li H, You C. The Accuracy of the Spot Sign and the Blend Sign for Predicting Hematoma Expansion in Patients with Spontaneous Intracerebral Hemorrhage. Med Sci Monit. 2017 May 12;23:2250-2257. PubMed PMID: 28498827; PubMed Central PMCID: PMC5437917.
9)

Yu Z, Zheng J, Ma L, Guo R, Li M, Wang X, Lin S, Li H, You C. The predictive accuracy of the black hole sign and the spot sign for hematoma expansion in patients with spontaneous intracerebral hemorrhage. Neurol Sci. 2017 Jun 2. doi: 10.1007/s10072-017-3006-6. [Epub ahead of print] PubMed PMID: 28577268.
10)

Yu Z, Zheng J, Ali H, Guo R, Li M, Wang X, Ma L, Li H, You C. Significance of satellite sign and spot sign in predicting hematoma expansion in spontaneous intracerebral hemorrhage. Clin Neurol Neurosurg. 2017 Sep 20;162:67-71. doi: 10.1016/j.clineuro.2017.09.008. [Epub ahead of print] PubMed PMID: 28946021.

Update: Cerebellopontine angle metastases

Cerebellopontine angle metastases

Metastatic lesions in the cerebellopontine angle (CPA) are rare and are commonly associated with breast cancer or lung cancer.

In a retrospective series of 1345 patients with CPA lesions the common underlying diagnoses were VS (91.3%), meningiomas (3.1%), epidermoids (2.4%) and facial nerve schwannomas (1.2%). Other rare causes (2%) included lipomas, gliomas, dermoids, arachnoid cysts, hemangiomas, hemangioblastomas, medulloblastomas, chondrosarcomas, malignant teratomas and metastasis 1).

Clinical features

Isolated metastases to the CPA represent a diagnostic challenge to differentiate them from the more commonly occurring CPA lesions, particularly in the absence of metastatic disease 2).

In a small series of 14 patients with metastasis to the CPA, this was the initial presentation of the underlying malignancy in 4 (28%) 3).

Features suggestive of metastasis as opposed to schwannoma were acute onset, rapid progression of symptoms, associated seventh and/or eighth nerve deficits, bilateral involvement or systemic metastasis. Useful MRI findings included small and/or bilateral CPA enhancing lesions with relative isointensity to brain parenchyma on pre-contrast MRI and associated findings of multiple and/or bilateral cranial nerve and/or leptomeningeal lesions 4).

Case series

2017

Ten patients were reviewed for the period between 2008 and 2015. The clinical and neuroimaging features, and treatment outcomes were analyzed retrospectively. The average period during primary diagnosis through the diagnosis of CPA metastases was 42.4 months. Among the 10 cases, the primary tumors and metastases were found simultaneously in 3 cases, the metastases after primary tumor removal were found in 5 cases, and the metastases after stereotaxic radiosurgery were found in 2 cases. Only 4 patients presented with the symptoms and signs associated with CPA involving, one with hearing loss, one presenting facial paralysis, one suffering from tinnitus and one case with dizziness. There were 2 cases with the miliary metastases and 8 cases with massive metastases. There existed 3 cases with single CPA metastases, whereas 7 cases with multiple metastatic foci. Among the 8 cases of massive metastatic foci, 6 tumors presented the solid features and the other 2 cases exhibited cystic and solid features. In this cohort of cases, 4 cases were involved in the bilateral and 6 cases presented unilateral metastatic foci. The three CPA metastases were removed in this group, 6 case performed with radiotherapy, and 5 cases received chemotherapy. In the current group 5 patients have been dead, 3 patients kept stable and 2 cases experienced improvement. In spite of seldom previous reports regarding the metastases from CNS tumors occurring in the CPA are existent, this rare form of the disease should be considered in future evaluation as a differential diagnosis 5).

2002

A total of 174 cancer patients with inner ear-related symptoms such as vertigo, hearing loss, or tinnitus were seen at the university hospital from January 1994 to December 2000. All patients underwent a battery of audiologic and neurotologic tests. Magnetic resonance imaging was performed either when the clinical presentation suggested vertigo of central origin or when sensorineural hearing loss developed.

Magnetic resonance imaging confirmed tumors of the cerebellopontine angle in 6 (3%) of the 174 patients, including 3 men and 3 women. Their ages ranged from 46 to 80 years (mean 62 years). The final diagnoses were breast cancer with cerebellopontine angle metastasis (1), breast cancer with cerebellopontine angle epidermoid cyst (1), colon cancer with cerebellopontine angle metastasis (1), colon cancer with acoustic neuroma (1), nasopharyngeal carcinoma with cerebellopontine angle metastasis (1), and nasopharyngeal carcinoma with cerebellopontine angle benign tumor (1).

When a cerebellopontine angle tumor is discovered in a cancer patient, metastatic cancer should be suspected when the tumor presents with deficits of the VIIth and VIIIth cranial nerves of rapid progression or bilateral involvement, or extracranial systemic metastasis. Laboratory examinations such as cytologic study of the cerebrospinal fluid and serologic study can assist in the diagnosis 6).

Case reports

2016

A 61-year-old man, who visited an otorhinolaryngology clinic with complaints of rapidly progressing bilateral hearing impairment and facial palsy. The patient was referred to our hospital because tumorous lesions were suspected in the bilateral cerebellopontine angles on brain magnetic resonance imaging. Regarding tumor markers, the patient’s cancer antigen 19-9 and carcinoembryonic antigen levels were high, which suggested metastasis. However, no abnormal findings other than abdominal lymph node enlargement were detected on whole-body examination, and no primary lesion was identified. The tumor in the right cerebellopontine angle was excised using the lateral suboccipital approach and subjected to pathological examination. It was diagnosed as an adenocarcinoma; thus, both lesions were considered brain metastases from a malignant abdominal tumor, and radiochemotherapy was administered to the patient. Unfortunately, the patient died after 89 days of treatment, and a pathological autopsy revealed that the primary lesion was a common bile duct tumor. No dural metastasis was noted in the brain or spinal cord; however, tumors were detected in the epiarachnoid space during surgery. Metastasis to the bilateral cerebellopontine angles occurred in the same period, which was indicative of ascending metastasis through the vertebrobasilar artery. Hence, we suggest that progressive bilateral hearing impairment and facial palsy were a consequence of brain tumors that had metastasized bilaterally to the cerebellopontine angles 7).

2015

A 63-year-old male who underwent surgical resection of a poorly differentiated small cell carcinoma, likely from a small intestinal primary tumor that metastasized to the cerebellopontine angle (CPA). A 63-year-old male presented with mild left facial paralysis, hearing loss, and balance instability. MRI revealed a 15 mm mass in the left CPA involving the internal auditory canal consistent with a vestibular schwannoma. Preoperative MRI eight weeks later demonstrated marked enlargement to 35 mm. The patient underwent a suboccipital craniectomy and the mass was grossly different visually and in consistency from a standard vestibular schwannoma. The final pathology revealed a poorly differentiated small cell carcinoma. Postoperative PET scan identified avid uptake in the small intestine suggestive of either a small intestinal primary tumor or additional metastatic disease. The patient underwent whole brain radiation therapy and chemotherapy and at last follow-up demonstrated improvement in his symptoms. Surgical resection and radiotherapy are potential treatment options to improve survival in patients diagnosed with NET brain metastases. We present the first documented case of skull base metastasis of a poorly differentiated small cell carcinoma involving the CPA 8).

2005

This is the first formal case report of internal auditory canal and cerebellopontine angle metastasis from infiltrative ductal carcinoma of the breast. Only three previous cases have been reported of isolated metastasis in the cerebellopontine angle and internal auditory canal from breast cancer. Currently, no therapeutic guidelines for isolated metastasis from breast cancer in this location exist. We report a case and review the current literature in order to help characterize the clinicopathologic features and management. A 72-year-old female with a 5-year history of left infiltrative ductal carcinoma of the breast reported progressive left-sided facial palsy and ipsilateral hearing loss accompanied by the development of tinnitus and unsteadiness during the previous 3 months. MRI identified a lesion in the cerebellopontine angle and internal auditory canal. The lesion was completely excised via a retrosigmoidal approach and adjuvant radiotherapy was used subsequently. The patient remains well 18 months after treatment, with no evidence of recurrence on repeat MRI. The rapid evolution of symptoms involving the Vth, VIIth or VIIIth cranial nerve, or multiple cranial nerves, is suggestive of a malignant lesion of the cerebellopontine angle and/or internal auditory canal. A previous history of neoplasm is important due to the possibility of a metastasis. Cerebellopontine angle metastasis can be found many years after the initial diagnosis of breast neoplasm. Surgery and adjuvant radiotherapy seems to be a good choice for the treatment of patients with this specific type of metastasis9).


Bilateral cerebellopontine angle (CPA) tumors identified on MRI are considered bilateral acoustic neuromas, the definitive diagnostic criterion of neurofibromatosis 2 (NF-2). We report the case of a 67-year-old man with progressive bilateral hearing loss, vertigo, and imbalance. MRI revealed bilateral enhancing CPA lesions, which were suggestive of acoustic neuromas and a diagnosis of NF-2. However, autopsy showed metastatic adenocarcinoma of the lung. Therefore, metastatic carcinoma to the CPA can mimic bilateral acoustic neuromas; imaging studies alone may be insufficient to diagnose NF-2 10).

1)

Brackmann DE, Bartels LJ. Rare tumors of the cerebellopontine angle. Otolaryngol Head Neck Surg (1979). 1980 Sep-Oct;88(5):555-9. PubMed PMID: 6969383.

2)

Hamid B, Harris C, Spiess J. Metastatic adenocarcinoma in the cerebellopontine angle mimicking facial nerve Schwannoma. Am J Clin Oncol. 2007 Oct;30(5):566-7. PubMed PMID: 17921722.

3)

Yuh WT, Mayr-Yuh NA, Koci TM, Simon JH, Nelson KL, Zyroff J, Jinkins JR. Metastatic lesions involving the cerebellopontine angle. AJNR Am J Neuroradiol. 1993 Jan-Feb;14(1):99-106. PubMed PMID: 8427116.

4)

Chiong Y, Mulroy L, Fleetwood IG, Younis T. Isolated metastasis to the cerebellopontine angle secondary to breast cancer. Can J Surg. 2009 Oct;52(5):E213-4. PubMed PMID: 19865565; PubMed Central PMCID: PMC2769124.

5)

Zhang M, Wang Z, Zhang J, Zhang H, Gu C, Wang H, Yu C, Wu H. Metastases in cerebellopontine angle from the tumors of central nerve system. J Clin Neurosci. 2017 Aug;42:84-90. doi: 10.1016/j.jocn.2017.04.011. Epub 2017 Apr 22. PubMed PMID: 28442197.

6)

Huang TW, Young YH. Differentiation between cerebellopontine angle tumors in cancer patients. Otol Neurotol. 2002 Nov;23(6):975-9. PubMed PMID: 12438865.

7)

Node Y, Harada N, Masuda H, Kondo K, Nemoto M, Sugo N. [A Rare Case of Metastatic Brain Tumors in the Bilateral Cerebellopontine Angles]. No Shinkei Geka. 2016 Dec;44(12):1033-1038. Japanese. PubMed PMID: 27932747.

8)

Theodros D, Goodwin CR, Crane GM, Liauw J, Kleinberg L, Lim M. Metastatic extrapulmonary small cell carcinoma to the cerebellopontine angle: a case report and review of the literature. Case Rep Oncol Med. 2015;2015:847058. doi: 10.1155/2015/847058. Epub 2015 Feb 25. PubMed PMID: 25810937; PubMed Central PMCID: PMC4355812.

9)

Guilemany JM, Alobid I, Gastón F, Morrelló A, Bernal-Sprekelsen M. Cerebellopontine angle and internal auditory canal metastasis from ductal carcinoma of the breast. Acta Otolaryngol. 2005 Sep;125(9):1004-7. PubMed PMID: 16193592.

10)

Hariharan S, Zhu J, Nadkarni MA, Donahue JE. Metastatic lung cancer in the cerebellopontine angles mimicking bilateral acoustic neuroma. J Clin Neurosci. 2005 Feb;12(2):184-6. PubMed PMID: 15749427.

Update: Falcotentorial meningioma treatment

Falcotentorial meningioma treatment

The primary aim of surgical treatment for falcotentorial meningiomas is gross total excision. The vital surrounding brain structures make this a complex task.

Several surgical approaches have been described to treat falcotentorial meningiomas. These include infratentorial supracerebellar approachsuboccipital approachoccipital transtentorial approach, and combined supratentorial and infratentorial approaches 1) 2) 3).

There are two main issues in treating falcotentorial meningiomas. One is selecting the surgical approach, which includes design of the bone flap. The other main issue is whether main venous structures will be sacrificed for a radical tumor resection.

In all of the cases, Hong et al. tried to make an adequately sized bone flap, even when the tumor was quite large. Some authors have insisted on performing wide craniotomies for large falcotentorial meningiomas 4).

Quiñones-Hinojosa, et al. 5) described a bilateral occipital transtentorial/transfalcine approach for large falcotentorial meningiomas. They ligated and cut the transverse sinus after checking the patency of the occluded sinus, and used permanent aneurysmal clips to ligate the vein of Galenwhen the straight sinus was occluded. The area above and below the tentorium can provide wide exposure and reduce occipital lobe retraction during prolonged operation times. Moreover, this approach may allow surgeons some form of intraoperative flexibility in terms of their surgical plan.

Hong et al. do not suggest routine application of wide craniotomies, such as the combined supratentorial and infratentorial approach. This is because wide craniotomies may increase the total amount of bleeding, prolong the operation time, and increase the risk of cerebral cortex injury. Moreover, it is possible to completely remove huge falcotentorial meningiomas without neurological deficit via relatively small craniotomies.

A catheter for CSF drainage was inserted into the ventricle or cisternal space through the safest area in each patient. They also designed small craniotomies through which the possible access area covered the entire tumor territory. Thus, if a CSF drain is possible, then appropriately designed small craniotomies are sufficient to achieve complete tumor resection without cortex injury 6).

There are some reports that have described usage of ligation and sectioning of the transverse sinus with or without reanastomosis 7) 8).

Although many authors have reported safe ligation of the transverse-sigmoid sinus, some complications have been described 9) 10).

Every venous structure should be preserved even if they seem to lack significant function. This will help prevent complications associated with delayed lobar parenchymal hemorrhage that can be attributed to venous infarction.

In conclusion, surgical approaches should be tailored to each patient according to the origin and direction of tumor growth, feeding arteries, and the surrounding venous drainage system.

Hong et al. found that a relatively small craniotomy was sufficient to completely remove each tumor. Moreover, they found that the most important factors for avoiding surgical complications were to preserve vital deep neurovascular structures, as well as flow through the venous sinuses.

The results showed that falcotentorial meningiomas could be cured via single-stage operations without complications by applying careful perioperative planning and a delicate microsurgical technique 11).

Videos


In this operative video, the authors demonstrate an illustrative step-by-step technique for endoscopic-assisted microsurgical resection of a falcotentorial meningioma using the posterior interhemispheric retrocallosal transfalcine approach for a superiorly positioned falcotentorial meningioma. The surgical nuances are discussed, including the surgical anatomy, gravity-assisted interhemispheric approach in the lateral position, retrocallosal dissection, transfalcine exposure, tumor removal, and preservation of the vein of Galen complex. In summary, the posterior interhemispheric retrocallosal transfalcine approach is a useful surgical strategy for select superiorly positioned falcotentorial meningiomas.

Case series

2009

From 2001 to 2005, 9 patients underwent operation for meningiomas arising from the falcotentorial junction, with some extending to and/or invading the torcula. All patients were assessed preoperatively with magnetic resonance neuroimaging and cerebral angiography. Furthermore, preoperative embolization was attempted in all cases. A supratentorial/infratentorial torcular craniotomy technique was used in all but 1 of these cases.

The average dimensions of the falcotentorial meningiomas were 5.1 x 4.4 x 4.2 cm. The angiograms revealed that these tumors were fed by branches of the internal carotid artery, choroidal arteries, branches of the meningohypophyseal trunk, and branches of the posterior cerebral artery. Preoperative embolization was achieved in only 2 patients. Five patients had gross total resection (Simpson grade 1), and 4 had subtotal resection (Simpson grade 4). Two of the tumors (22%) recurred during a mean follow-up period of 49 months (range, 17-88 months). The most common complication after surgery was cortical blindness, but all postoperative visual deficits had fully recovered at the last follow-up evaluation within several months.

An excellent outcome can be expected with detailed preoperative neuroimaging and knowledge of the nuances of the surgical technique that we describe in detail in the article 12).

2006

Goto et al. evaluated their surgical experience over 20 years with 14 treated falcotentorial meningiomas.

In the past 20 years, 14 patients with falcotentorial junction meningiomas were surgically treated. There were seven men and seven women, whose ages ranged from 34 to 79 years. On the basis of neuroimaging studies, the authors analyzed the influence of the anatomical relationship of the tumor to the vein of Galen, patency of the vein of Galen, tumor size, and the signal intensities on the magnetic resonance images to determine possible difficulties that might be encountered during surgery and to prognosticate the outcome of surgery. Depending on the relationship with the vein of Galen, tumors were labeled as either a superior or an inferior type. All tumors were resected via an occipital transtentorial approach. The surgical outcome in eight patients was excellent; in the remaining six patients, it was fair. Of the prognostic factors, tumor location especially seemed to be the most important (p < 0.01, Fisher exact test). The outcome associated with the inferior type of tumor was significantly less optimal probably due to the relationship to the deep veins and the brainstem. In this series, the occlusion of deep veins did not significantly influence outcome.

Classification of the tumor location by preoperative neuroimaging studies can be helpful in estimating the surgical difficulty that might be encountered in treating the falcotentorial junction meningioma 13).

2003

Meningiomas arising from the falcotentorial junction are rare. As a result, their clinical presentation and surgical management are not well described. During the past 3 years, the authors have treated six patients with falcotentorial meningiomas.

Most patients presented with symptoms related to raised intracranial pressure, including headaches, papilledema, and visual and gait disturbances. Magnetic resonance imaging revealed a smooth, oval, or round mass, which was typically homogeneously enhancing. Angiography was useful in evaluating arterial supply for embolization, when possible, and determining the status of venous collateral supply and sinus patency. The authors detail the surgical technique used in all six patients. Postoperatively, patients experienced transient cortical blindness, which in all cases spontaneously resolved during the course of several days to weeks. They provide a comprehensive description of the presentation and surgical management of falcotentorial meningiomas.

An excellent outcome can be expected when surgery is predicated on detailed preoperative neuroimaging and knowledge of the nuances of the surgical technique 14).

2001

Okami et al. present four surgical cases. An occipital transtentorial approach was used in three cases, and a combined midline occipital and suboccipital approach in one case. Total tumour excision was impossible in two cases because of engulfing deep venous structures including the great vein of Galen. Postoperative Gamma knife radiosurgery was performed in these two cases. On the other hand, a posteriorly located tumour was relatively easy to remove, and macroscopic total removal was accomplished. In conclusion, precise microvascular anatomical knowledge is indispensable to satisfactorily excise meningiomas in the falcotentorial area without significant morbidity 15).

1995

Asari et al. describe the clinical features, neuroimaging studies, and results of surgical treatment of meningiomas of the falcotentorial junction and clarify the characteristics of this lesion based on a review of the literature and seven patients treated at their institution. The most common symptoms resulted from intracranial hypertension. Upward-gaze palsy appeared in only one patient. Computerized tomography (CT) showed no specific findings, but there was no evidence of edema around the tumor. Magnetic resonance (MR) imaging revealed a round, smooth-bordered mass with a peritumoral rim, without edema, and showing marked contrast enhancement. The multiplanar capability of MR imaging delineated the relationship between the tumor and adjacent structures better than did CT. Detailed knowledge of the vascular structures, especially evidence of occlusion of the galenic venous system and the development of collateral venous channels, is critical for successful surgery; stereoscopic cerebral angiography is necessary to achieve this aim. The seven patients described developed five types of collateral venous channels: through the basal vein of Rosenthal to the petrosal vein, through the veins on the medial surface of the parietal and occipital lobes to the superior sagittal sinus, through superficial anastomotic veins, through veins of the posterior fossa to the transverse or straight sinus, and through the falcian veins to the superior sagittal sinus. The first three types mainly developed after occlusion of the galenic system. The tumors were removed through the occipital transtentorial approach with a large window at the posterior part of the falx. A favorable prognosis for patients undergoing surgical treatment of falcotentorial junction meningiomas can be expected if detailed neuroimaging studies and microsurgical techniques are used 16).


The tumors were removed subtotally or totally via an occipital interhemispheric transtentorial approach and/or infratentorial supracerebellar approach. The postoperative courses were uneventful, and no neurological deficit was detected postoperatively. Pineal region tumors with a maximum diameter of 5 cm or larger should be operated on via a unilateral or bilateral occipital interhemispheric transtentorial approach, regardless of the angiographic findings, because this permits a wide operative field and can be followed, if necessary, by an infratentorial supracerebellar approach. Selection of the operative approach for a relatively small pineal region tumor should depend on the angiographic findings: downward displacement of the bilateral internal cerebral veins and the great vein of Galen indicates an occipital interhemispheric transtentorial approach, whereas upward displacement indicates an infratentorial supracerebellar approach 17).

Case reports

2017

One representative case of falcotentorial meningioma treated through an anterior interhemispheric transsplenial approach is also described. Among the interhemispheric approaches to the pineal region, the anterior interhemispheric transsplenial approach has several advantages. 1) There are few or no bridging veins at the level of the pericoronal suture. 2) The parietal and occipital lobes are not retracted, which reduces the chances of approach-related morbidity, especially in the dominant hemisphere. 3) The risk of damage to the deep venous structures is low because the tumor surface reached first is relatively vein free. 4) The internal cerebral veins can be manipulated and dissected away laterally through the anterior interhemispheric route but not via the posterior interhemispheric route. 5) Early control of medial posterior choroidal arteries is obtained. The anterior interhemispheric transsplenial approach provides a safe and effective surgical corridor for patients with supratentorial pineal region tumors that 1) extend superiorly, involve the splenium of the corpus callosum, and push the deep venous system in a posterosuperior or an anteroinferior direction; 2) are tentorial and displace the deep venous system inferiorly; or 3) originate from the splenium of the corpus callosum 18).

2006

Kawashima et al. reported, in anatomic studies, a occipital transtentorial approach: the occipital bi-transtentorial/falcine approach, to treat such lesions. Gusmão et al. present a patient with a large falcotentorial meningioma, located bilaterally in the posterior incisural space. The occipital bi-transtentorial/falcine approach allowed an excellent surgical exposure and complete tumor removal with an excellent patient outcome 19).

References

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Okami N, Kawamata T, Hori T, Takakura K. Surgical treatment of falcotentorial meningioma. J Clin Neurosci. 2001 May;8 Suppl 1:15-8. Review. PubMed PMID: 11386819.
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Raco A, Agrillo A, Ruggeri A, Gagliardi FM, Cantore G. Surgical options in the management of falcotentorial meningiomas: report of 13 cases. Surg Neurol. 2004 Feb;61(2):157-64; discussion 164. PubMed PMID: 14751629.
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Sekhar LN, Goel A. Combined supratentorial and infratentorial approach to large pineal-region meningioma. Surg Neurol. 1992 Mar;37(3):197-201. PubMed PMID: 1536024.
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Hong CK, Hong JB, Park H, Moon JH, Chang JH, Lee KS, Park SW. Surgical Treatment for Falcotentorial Meningiomas. Yonsei Med J. 2016 Jul;57(4):1022-8. doi: 10.3349/ymj.2016.57.4.1022. PubMed PMID: 27189300; PubMed Central PMCID: PMC4951445.
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Quiñones-Hinojosa A, Chang EF, Chaichana KL, McDermott MW. Surgical considerations in the management of falcotentorial meningiomas: advantages of the bilateral occipital transtentorial/transfalcine craniotomy for large tumors. Neurosurgery. 2009 May;64(5 Suppl 2):260-8; discussion 268. doi: 10.1227/01.NEU.0000344642.98597.A7. PubMed PMID: 19287325.
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Hwang SK, Gwak HS, Paek SH, Kim DG, Jung HW. Guidelines for the ligation of the sigmoid or transverse sinus during large petroclival meningioma surgery. Skull Base. 2004 Feb;14(1):21-8; discussion 29. PubMed PMID: 16145581; PubMed Central PMCID: PMC1151668.
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Al-Mefty O, Fox JL, Smith RR. Petrosal approach for petroclival meningiomas. Neurosurgery. 1988 Mar;22(3):510-7. PubMed PMID: 3362317.
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Hitselberger WE, House WF. A combined approach to the cerebellopontine angle. A suboccipital-petrosal approach. Arch Otolaryngol. 1966 Sep;84(3):267-85. PubMed PMID: 5296435.
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Goto T, Ohata K, Morino M, Takami T, Tsuyuguchi N, Nishio A, Hara M. Falcotentorial meningioma: surgical outcome in 14 patients. J Neurosurg. 2006 Jan;104(1):47-53. PubMed PMID: 16509146.
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Quinones-Hinojosa A, Chang EF, McDermott MW. Falcotentorial meningiomas: clinical, neuroimaging, and surgical features in six patients. Neurosurg Focus. 2003 Jun 15;14(6):e11. Review. PubMed PMID: 15669786.
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Asari S, Maeshiro T, Tomita S, Kawauchi M, Yabuno N, Kinugasa K, Ohmoto T. Meningiomas arising from the falcotentorial junction. Clinical features, neuroimaging studies, and surgical treatment. J Neurosurg. 1995 May;82(5):726-38. Review. PubMed PMID: 7714596.
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Matsuda Y, Inagawa T. Surgical removal of pineal region meningioma–three case reports. Neurol Med Chir (Tokyo). 1995 Aug;35(8):594-7. PubMed PMID: 7566392.
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Yağmurlu K, Zaidi HA, Kalani MY, Rhoton AL Jr, Preul MC, Spetzler RF. Anterior interhemispheric transsplenial approach to pineal region tumors: anatomical study and illustrative case. J Neurosurg. 2017 Jan 13:1-11. doi: 10.3171/2016.9.JNS16279. [Epub ahead of print] PubMed PMID: 28084911.
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Gusmão S, Oliveira MM, Arantes A, Ulhoa TH, Morato EG. Occipital bi-transtentorial/falcine approach for falcotentorial meningioma: case report. Arq Neuropsiquiatr. 2006 Mar;64(1):136-8. Epub 2006 Apr 5. PubMed PMID: 16622571.

Update: Anticonvulsant in aneurysmal subarachnoid hemorrhage

Anticonvulsant in aneurysmal subarachnoid hemorrhage

Concerns over the possible consequences of a seizure in the setting of an unsecured intracranial aneurysm, has led to routine prophylactic administration of antiepileptic drugs (AEDs) following SAH in many centers 1) 2).

In a review, the Department of Clinical Pharmacy, University of Tennessee Health Science Center, College of Pharmacy, Knoxville, describes the evidence associated with the use of AEDs for seizure prophylaxis in patients with intracerebral tumors, traumatic brain injury, aneurysmal subarachnoid hemorrhage, craniotomy, ischemic stroke, and intracerebral hemorrhage. Clear evidence indicates that the short-term use of AEDs for seizure prophylaxis in patients with traumatic brain injury and aneurysmal subarachnoid hemorrhage may be beneficial; however, evidence to support the use of AEDs in other disease states is less clear 3).

Anticonvulsant prophylaxis remains controversial, with studies suggesting a brief course may be adequate and longer exposure may be associated with worse outcomes. Nonetheless, in the absence of controlled trials to inform practice, patients continue to receive variable chemoprophylaxis 4).

Current practice regarding seizure prophylaxis in aneurysmal subarachnoid hemorrhage across academic centers

An eight question survey was sent to 25 US centers with high volume aSAH cases (>100 annually). Respondents were asked about institutional practices regarding use, duration, and type of seizure prophylaxis.

13 (52%) respondents endorsed the utility of seizure prophylaxis while 10 (40%) did not, and two (8%) were unsure. Among respondents using prophylaxis, levetiracetam was the firstline medication for the majority (94%) while phenytoin was used as a primary agent at one (4%) center and as a secondary agent at four (16%) centers. Duration of levetiracetam prophylaxis ranged from 1 day to 6 weeks following SAH (mean 13.2; median 11). Only a single center employed EEG routinely in all aSAH patients but most supported EEG use when the neurologic examination was unreliable or inexplicably declining. 24 (96%) respondents agreed that a trial randomizing patients to levetiracetam or no antiseizure medication is warranted at this time, and all 25 (100%) believed that such a trial would be appropriate or ethically sound.

The routine use of seizure prophylaxis following aSAH is controversial. Among a sampling of 25 major academic centers, most administer prophylaxis, while a significant proportion does not. The majority believes a trial randomizing patients to receive seizure prophylaxis is both timely and ethical 5)

Complications

Literature has suggested increased adverse effects associated with post-hemorrhagic AED exposure; including serious drug related complications as well as worse cognitive and functional outcomes 6).

Up to 21% of those receiving AED prophylaxis suffered adverse medication side effects, including impaired liver function, thrombocytopenia, rash, and Stevens-Johnson syndrome. Few studies to date have specifically evaluated prophylactic AED treatment protocols, and only one has detailed the incidence and risk factors of clinical seizures in patients not receiving prophylactic AED medications 7).

Reviews

2013

Raper et al. performed a MEDLINE (1985-2011) search to identify randomized controlled trials and retrospective series of aSAH. Statistical analyses of categorical variables such as presentation and early and late seizures were carried out using χ(2) and Fisher exact tests.

They included 25 studies involving 7002 patients. The rate of early postoperative seizure was 2.3%. The rate of late postoperative seizure was 5.5%. The average time to late seizure was 7.45 months. Patients who experienced a late seizure were more likely to have MCA aneurysms, be Hunt/Hess grade III, and be repaired with microsurgical clipping than endovascular coiling.

Despite improved microsurgical techniques and antiepileptic drug prophylaxis, a significant proportion of patients undergoing aneurysm clipping still experience seizures. Seizures may occur years after aneurysm repair, and careful monitoring for late complications remains important. Furthermore, routine perioperative AED use does not seem to prevent seizures after SAH 8).


Marigold et al. searched the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1) in The Cochrane Library, and MEDLINE (1946 to 12th March 2013). We checked the reference lists of articles retrieved from these searches.

They considered all randomised and quasi-randomised controlled trials in which patients were assigned to a treatment (one or more AEDs) or placebo.

Two review authors (RM and JK) independently screened and assessed the methodological quality of the studies. If studies were included, one author extracted the data and the other checked it.

No relevant studies were found.

There was no evidence to support or refute the use of antiepileptic drugs for the primary or secondary prevention of seizures related to subarachnoid haemorrhage. Well-designed randomised controlled trials are urgently needed to guide clinical practice 9).

2011

An electronic literature search was conducted for English language articles describing the incidence and treatment of seizures after aneurysmal subarachnoid hemorrhage from 1980 to October 2010. A total of 56 articles were included in this review. Seizures often occur at the time of initial presentation or aneurysmal rebleeding before aneurysm treatment. Seizures occur in about 2% of patients after invasive aneurysm treatment, with a higher incidence after surgical clipping compared with endovascular repair. Non-convulsive seizures should be considered in patients with poor neurological status or deterioration. Seizure prophylaxis with antiepileptic drugs is controversial, with limited data available for developing recommendations. While antiepileptic drug use has been linked to worse prognosis, studies have evaluated treatment with almost exclusively phenytoin. When prophylaxis is used, 3-day treatment seems to provide similar seizure prevention with better outcome compared with longer-term treatment 10).

2010

The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom line conclusions. Neurology consultants and residents, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy, neurosurgery, and critical care contributed to the review and placed the evidence in clinical context.

There were no relevant randomized, controlled trials that addressed the question. A post hoc analysis of data from 4 trials of tirilazad for aSAH showed that prophylactic AED therapy was associated with worse Glasgow Outcome Scale scores at 3 months (odds ratio 1.56, 95% confidence interval 1.16-2.10; P = 0.003) but numerous confounders limit data interpretation.

There are insufficient data to support or refute the prophylactic use of AED therapy after aSAH. Randomized, controlled trials are needed to address the efficacy and risks of AEDs in this setting and should take into account factors such as aneurysmal factors (location, hemorrhage grade, degree of parenchymal injury), type of aneurysm surgery (clip vs. coil), and evaluate the timing and duration of AED use 11).

Case series

2017

Human et al. performed a prospective, single-center, randomized, open-label trial of a brief (3-day) course of levetiracetam (LEV) versus extended treatment (until hospital discharge). The primary outcome was in-hospital seizure. Secondary outcomes included drug discontinuation and functional outcome.

Eighty-four SAH patients had been randomized when the trial was terminated due to slow enrollment. In-hospital seizures occurred in three (9%) of 35 in the brief LEV group versus one (2%) of 49 in the extended group (p = 0.2). Ten (20%) of the extended group discontinued LEV prematurely, primarily due to sedation. Four of five seizures (including one pre-randomization) occurred in patients with early brain injury (EBI) on computed tomography (CT) scans (adjusted OR 12.5, 95% CI 1.2-122, p = 0.03). Good functional outcome (mRS 0-2) was more likely in the brief LEV group (83 vs. 61%, p = 0.04).

This study was underpowered to demonstrate superiority of extended LEV for seizure prophylaxis, although a trend to benefit was seen. Seizures primarily occurred in those with radiographic EBI, suggesting targeted prophylaxis may be preferable. Larger trials are required to evaluate optimal chemoprophylaxis in SAH, especially in light of worse outcomes in those receiving extended treatment 12).

2016

Panczykowski et al.retrospectively analyzed a prospectively collected database of subarachnoid hemorrhage patients admitted to the Department of Neurological Surgery, University of Pittsburgh Medical Center,

Between 2005 and 2007, all patients received prophylactic AEDs upon admission. After 2007, no patients received prophylactic AEDs or had AEDs immediately discontinued if initiated at an outside hospital. A propensity score-matched analysis was then performed to compare the development of clinical and electrographic seizures in these 2 populations.

Three hundred and fifty three patients with spontaneous subarachnoid hemorrhage were analyzed, 43% of whom were treated with prophylactic AEDs upon admission. Overall, 10% of patients suffered clinical and electrographic seizures, most frequently occurring within 24 hours of ictus (47%). The incidence of seizures did not vary significantly based on the use of prophylactic AEDs (11 versus 8%; P=0.33). Propensity score-matched analyses suggest that patients receiving prophylactic AEDs had a similar likelihood of suffering seizures as those who did not (P=0.49).

Propensity score-matched analysis suggests that prophylactic AEDs do not significantly reduce the risk of seizure occurrence in patients with spontaneous subarachnoid hemorrhage 13).

2014

Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. The objective of Karamchandani was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated 14).

2013

Exploratory analysis was performed on 413 patients enrolled in CONSCIOUS-1 (Clazosentan to Overcome Neurological Ischemia and Infarction Occurring after Subarachnoid Hemorrhage), a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm. The association among clinical, laboratory, and radiographic covariates and the occurrence of seizures following SAH were determined. Covariates with a significance level of p < 0.20 on univariate analysis were entered into a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was used to define optimal predictive thresholds.

Of the 413 patients enrolled in the study, 57 (13.8%) had at least 1 seizure following SAH. On univariate analysis, a World Federation of Neurosurgical Societies grade of IV-V, a greater subarachnoid clot burden, and the presence of midline shift and subdural hematomas were associated with seizure activity. On multivariate analysis, only a subarachnoid clot burden (OR 2.76, 95% CI 1.39-5.49) and subdural hematoma (OR 5.67, 95% CI 1.56-20.57) were associated with seizures following SAH. Using ROC curve analysis, the optimal predictive cutoff for subarachnoid clot burden was determined to be 21 (of a possible 30) on the Hijdra scale (area under the curve 0.63).

A greater subarachnoid clot burden and subdural hematoma are associated with the occurrence of seizures after aneurysm rupture. These findings may help to identify patients at greatest risk for seizures and guide informed decisions regarding the prescription of prophylactic anticonvulsive therapy. Clinical trial registration no.: NCT00111085 (ClinicalTrials.gov) 15).

2008

A total of 137 adult patients were enrolled in this two-year retrospective study. Baseline prognostic variables were analyzed based on Cox’s proportional hazards model after a minimum of one-year follow-up.

Seizures occurred in 21 patients who had SAH, including acute symptomatic seizures in 11.7% (16/137) and unprovoked seizures in 3.6% (5/137). None progressed to status epilepticus during hospitalization. After a minimum of one-year follow-up, the mean Glasgow Outcome Score was 3.5 +/- 1.4 for patients with seizures and 3.1 +/- 1.1 for those without.

Higher mean World Federation of Neurological Societies grade on presentation was predictive of seizure, but seizure itself was not a significant prognostic predictor after a minimum of one-year follow-up. Regarding potential side effects of anti-epileptic drugs, anti-epileptic therapy should be carefully administered to patients with seizures after aneurysmal SAH 16).

2007

Rosengart et al. examined data collected in 3552 patients with SAH who were entered into four prospective, randomized, double-blind, placebo-controlled trials conducted in 162 neurosurgical centers and 21 countries between 1991 and 1997. The prevalence of AED use was assessed by study country and center. The impact of AEDs on in-hospital complications and outcome was evaluated using conditional logistic regressions comparing treated and untreated patients within the same study center.

Antiepileptic drugs were used in 65.1% of patients and the prescribing pattern was mainly dependent on the treating physicians: the prevalence of AED use varied dramatically across study country and center (intraclass correlation coefficients 0.22 and 0.66, respectively [p < 0.001]). Other predictors included younger age, worse neurological grade, and lower systolic blood pressure on admission. After adjustment, patients treated with AEDs had odds ratios of 1.56 (95% confidence interval [CI] 1.16-2.10; p = 0.003) for worse outcome based on the Glasgow Outcome Scale; 1.87 (95% CI 1.43-2.44; p < 0.001) for cerebral vasospasm; 1.61 (95% CI 1.25-2.06; p < 0.001) for neurological deterioration; 1.33 (95% CI 1.01-1.74; p = 0.04) for cerebral infarction; and 1.36 (95% CI 1.03-1.80; p = 0.03) for elevated temperature during hospitalization.

Prophylactic AED treatment in patients with aneurysmal SAH is common, follows an arbitrary prescribing pattern, and is associated with increased in-hospital complications and worse outcome 17).


From July 1998 to June 2002, 453 patients with spontaneous subarachnoid hemorrhage were treated. In the first 9 months, 79 patients were administered PHT until discharged from the hospital, unless a drug reaction occurred first. In the last 39 months, PHT was discontinued 3 days after admission (370 patients), unless there was a history of epilepsy (four patients). This study represents a retrospective analysis of prospectively collected data, with follow-up periods of 3 to 12 months after discharge. RESULTS: The 3-day PHT regimen produced a statistically significant reduction (P = 0.002) in the rate of PHT complications. In the first period, seven (8.8%) out of 79 patients experienced a hypersensitivity reaction, compared with two (0.5%) out of 370 patients in the second period. The percentage of patients having seizures, both short- and long-term, did not change significantly. In the first period, the seizure rate during hospitalization was 1.3%; in the second period, it was 1.9% (P = 0.603). At an average follow-up period of 6.7 months, three (5.7%) out of 53 survivors in the first period experienced a seizure (including those who had a seizure during hospitalization). In the second period, 12 (4.6%) out of 261 survivors experienced a seizure at an average follow-up period of 5.4 months (P = 0.573).

A 3-day regimen of PHT prophylaxis is adequate to prevent seizures in subarachnoid hemorrhage patients. Drug reactions are significantly reduced, but seizure rates do not change. Short-term PHT administration may be a superior treatment paradigm 18).

2005

Naidech et al. studied 527 SAH patients and calculated a “PHT burden” for each by multiplying the average serum level of PHT by the time in days between the first and last measurements, up to a maximum of 14 days from ictus. Functional outcome at 14 days and 3 months was measured with the modified Rankin scale, with poor functional outcome defined as dependence or worse (modified Rankin Scale > or =4). We assessed cognitive outcomes at 14 days and 3 months with the telephone interview for cognitive status. RESULTS: PHT burden was associated with poor functional outcome at 14 days (OR, 1.5 per quartile; 95% CI, 1.3 to 1.8; P<0.001), although not at 3 months (P=0.09); the effect remained (OR, 1.6 per quartile; 95% CI, 1.2 to 2.1; P<0.001) after correction for admission Glasgow Coma Scale, fever, stroke, age, National Institutes of Health Stroke Scale > or =10, hydrocephalus, clinical vasospasm, and aneurysm rebleeding. Seizure in hospital (OR, 4.1; 95% CI, 1.5 to 11.1; P=0.002) was associated with functional disability in a univariate model only. Higher quartiles of PHT burden were associated with worse telephone interview for cognitive status scores at hospital discharge (P<0.001) and at 3 months (P=0.003). CONCLUSIONS: Among patients treated with PHT, burden of exposure to PHT predicts poor neurologic and cognitive outcome after SAH 19).

2000

Rhoney et al. reviewed 95 SAH patient charts using standardized forms. Variables included prophylaxis duration, seizure incidence and timing, CT findings, AED adverse events, and 1-year patient follow-up.

Prehospital seizures occurred in 17.9% (17/95) of patients; another 7.4% (7/95) had a questionable prehospital seizure. In-hospital seizures occurred in 4.1% (4/95) of patients, a mean of 14.5 +/- 13.7 days from ictus; three of these four patients were receiving an AED at the time of seizure. Inpatient AED were prescribed to 99% of the cohort for a median of 12 (range 1 to 68) days. Approximately 8% of the cohort had posthospital discharge seizures; this included the patients who had prehospital or in-hospital seizures, 50% of whom were receiving AED therapy at the time of the seizure. Adverse effects occurred in 4. 1%; none were serious. The thickness of cisternal clot was associated with having a seizure; no other clinical predictors were identified. Having a seizure at any time did not adversely affect outcome.

In this SAH population, the majority of seizures happened before medical presentation. In-hospital seizures were rare and occurred more than 7 days postictus for patients receiving AED prophylaxis. The vast majority of putative clinical predictors did not help predict the occurrence of seizures; only the thickness of the cisternal clot was of value in predicting seizures. Patient selection for and the efficacy and timing of AED prophylaxis after SAH deserve prospective evaluation 20).

Experimental Studies

A study demonstrated that Valproic Acid (VPA) improves neurological outcome and decreases brain injury in a mouse model of SAH 21).

Recommendations

Dana G. Boeck, PharmD Department of Pharmacy, University Health System, San Antonio, Texas Division of Pharmacotherapy, The University of Texas at Austin College of Pharmacy Pharmacotherapy Education and Research Center University of Texas Health Science Center at San Antonio November 20, 2015 boeck11-20-15.pdf

1) , 18)

Chumnanvej S, Dunn IF, Kim DH. Three-day phenytoin prophylaxis is adequate after subarachnoid hemorrhage. Neurosurgery. 2007 Jan;60(1):99-102; discussion 102-3. PubMed PMID: 17228257.

2) , 8)

Raper DM, Starke RM, Komotar RJ, Allan R, Connolly ES Jr. Seizures after aneurysmal subarachnoid hemorrhage: a systematic review of outcomes. World Neurosurg. 2013 May-Jun;79(5-6):682-90. doi: 10.1016/j.wneu.2012.08.006. Epub 2012 Sep 25. Review. PubMed PMID: 23022642.

3)

Rowe AS, Goodwin H, Brophy GM, Bushwitz J, Castle A, Deen D, Johnson D, Lesch C, Liang N, Potter E, Roels C, Samaan K, Rhoney DH; Neurocritical Care Society Pharmacy Section. Seizure prophylaxis in neurocritical care: a review of evidence-based support. Pharmacotherapy. 2014;34(4):396-409. doi: 10.1002/phar.1374. Epub 2013 Nov 26. Review. PubMed PMID: 24277723.

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Human T, Diringer MN, Allen M, Zipfel GJ, Chicoine M, Dacey R, Dhar R. A Randomized Trial of Brief Versus Extended Seizure Prophylaxis After Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2017 Aug 22. doi: 10.1007/s12028-017-0440-5. [Epub ahead of print] PubMed PMID: 28831717.

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Dewan MC, Mocco J. Current practice regarding seizure prophylaxis in aneurysmal subarachnoid hemorrhage across academic centers. J Neurointerv Surg. 2015 Feb;7(2):146-9. doi: 10.1136/neurintsurg-2013-011075. Epub 2014 Jan 28. PubMed PMID: 24474163.

6) , 19)

Naidech AM, Kreiter KT, Janjua N, Ostapkovich N, Parra A, Commichau C, Connolly ES, Mayer SA, Fitzsimmons BF. Phenytoin exposure is associated with functional and cognitive disability after subarachnoid hemorrhage. Stroke. 2005 Mar;36(3):583-7. Epub 2005 Jan 20. PubMed PMID: 15662039.

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Lin YJ, Chang WN, Chang HW, Ho JT, Lee TC, Wang HC, Tsai NW, Tsai MH, Lu CH. Risk factors and outcome of seizures after spontaneous aneurysmal subarachnoid hemorrhage. Eur J Neurol. 2008 May;15(5):451-7. doi: 10.1111/j.1468-1331.2008.02096.x. Epub 2008 Mar 5. PubMed PMID: 18325027.

9)

Marigold R, Günther A, Tiwari D, Kwan J. Antiepileptic drugs for the primary and secondary prevention of seizures after subarachnoid haemorrhage. Cochrane Database Syst Rev. 2013 Jun 5;(6):CD008710. doi: 10.1002/14651858.CD008710.pub2. Review. PubMed PMID: 23740537.

10)

Lanzino G, D’Urso PI, Suarez J; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Seizures and anticonvulsants after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2011 Sep;15(2):247-56. doi: 10.1007/s12028-011-9584-x. Review. PubMed PMID: 21751102.

11)

Riordan KC, Wingerchuk DM, Wellik KE, Zimmerman RS, Sirven JI, Noe KH, Patel BM, Demaerschalk BM. Anticonvulsant drug therapy after aneurysmal subarachnoid hemorrhage: a critically appraised topic. Neurologist. 2010 Nov;16(6):397-9. doi: 10.1097/NRL.0b013e3181efc92f. PubMed PMID: 21150393.

13)

Panczykowski D, Pease M, Zhao Y, Weiner G, Ares W, Crago E, Jankowitz B, Ducruet AF. Prophylactic Antiepileptics and Seizure Incidence Following Subarachnoid Hemorrhage: A Propensity Score-Matched Analysis. Stroke. 2016 Jul;47(7):1754-60. doi: 10.1161/STROKEAHA.116.013766. Epub 2016 Jun 14. PubMed PMID: 27301932; PubMed Central PMCID: PMC4927347.

14)

Karamchandani RR, Fletcher JJ, Pandey AS, Rajajee V. Incidence of delayed seizures, delayed cerebral ischemia and poor outcome with the use of levetiracetam versus phenytoin after aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2014 Sep;21(9):1507-13. doi: 10.1016/j.jocn.2014.03.009. Epub 2014 Jun 3. PubMed PMID: 24919470.

15)

Ibrahim GM, Fallah A, Macdonald RL. Clinical, laboratory, and radiographic predictors of the occurrence of seizures following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2013 Aug;119(2):347-52. doi: 10.3171/2013.3.JNS122097. Epub 2013 Apr 12. PubMed PMID: 23581590.

17)

Rosengart AJ, Huo JD, Tolentino J, Novakovic RL, Frank JI, Goldenberg FD, Macdonald RL. Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs. J Neurosurg. 2007 Aug;107(2):253-60. PubMed PMID: 17695377.

20)

Rhoney DH, Tipps LB, Murry KR, Basham MC, Michael DB, Coplin WM. Anticonvulsant prophylaxis and timing of seizures after aneurysmal subarachnoid hemorrhage. Neurology. 2000 Jul 25;55(2):258-65. PubMed PMID: 10908901.

21)

Tso MK, Lass E, Ai J, Loch Macdonald R. Valproic Acid treatment after experimental subarachnoid hemorrhage. Acta Neurochir Suppl. 2015;120:81-5. doi: 10.1007/978-3-319-04981-6_14. PubMed PMID: 25366604.

Update: Middle cerebral artery M4 segment aneurysm

Middle cerebral artery M4 segment aneurysm

Middle cerebral artery aneurysms, are mainly found in the proximal and bifurcation tracts and only in the 1.1-1.7% of cases they are located in the M4 segment of the middle cerebral artery 1) 2) 3).

Etiology

Generally, these aneurysms are secondary to traumatic brain injury and inflammatory or infectious diseases and only rarely they have idiopathic origin 4). At present, only nine cases of ruptured cortical middle cerebral artery aneurysms have been described in literature 5) 6) 7) 8) 9) 10). The patients are all males, except the case of Ricci et al. 11). The average age of the reported patients is 40 years. The size of the aneurysms is between 1 mm and 10 mm and, in most cases, they are saccular intracranial aneurysms or fusiform morphology. In five patients, the aneurysms present infectious etiology. Usually, they occur with ICH, sometimes associated with subarachnoid hemorrhage (SAH).

Treatment

The endovascular treatment (EVT) has been performed in four cases, while the surgical treatment has been performed in three cases (two of trapping and one of clipping). In one patient, the infectious aneurysm has resolved spontaneously after antibiotic therapy. In all treatments performed, the patients have improved the neurologic symptoms and no residual aneurysms have been observed in the subsequent neuroradiology follow-up 12). Although surgery remains the main choice in the M4 aneurysms, because of the extremely distal location of them over the motor/somatosensory cortices, 13) Lv et al. 14) propose the use of the EVT in all types of the M4 aneurysms, especially after the surgery, when it is impossible to locate the small ruptured aneurysm. The main difficulty of the surgery is the precise surgical localization of the small M4 aneurysms 15). An inaccurate localization of these vascular lesions may result in larger craniotomies and unnecessary arachnoid and pial dissections with possible resultant permanent neurological injuries 16). In cases of aneurysms or arteriovenous malformations located at the sylvian point or at the posterior superior aspect of the insula, especially in dominant hemisphere, to reduce the dissection and open easily sylvian fissure, a logical path would follow the angular artery in the sylvian fissure cutting the arachnoid fibers and retracting only the tissues which are necessary to gain more exposure of the lesion 17).

Case reports

2017

A 53-year-old female was admitted with a sudden severe headache, nausea, vomiting, and a slight left hemiparesis. The computed tomography (CT) scan showed subarachnoid hemorrhage (SAH) in the left sylvian fissure and intracerebral hemorrhage (ICH) in the left posterior parietal area. The CT angiography (CTA) reconstructed with 3D imaging showed a small saccular aneurysm in the M4 segment in proximity of the angular area. A left parieto-temporal craniotomy was performed, the aneurysm was clipped and the ICH evacuated. The motor deficit was progressively recovered. At 3-month follow-up examination, the patient was asymptomatic and feeling well. Surgery is the best choice for the treatment of ruptured M4 aneurysms with ICH in the opinion of Ricci et al., because it allows to evacuate the hematoma and to exclude the aneurysm from the intracranial circulation. In addition, we suggest both the use of the neuronavigation technique and of the indocyanine green videoangiography (ICGV) for the aneurismal surgery 18).

2007

A 41-year-old man presented with an infarction manifesting as left-sided weakness and dysarthria. Magnetic resonance angiography revealed a subacute stage infarction in the right MCA territory and complete occlusion of the right ICA. Angiography demonstrated aneurysmal dilatation of the M4 segment of the right MCA. Surgery was performed to prevent hemorrhage from the aneurysm. The aneurysm was proximally clipped guided by Navigation-CT angiography and flow to the distal MCA was restored by superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis 19).

2005

A 20-year-old man with an intracerebral haemorrhage due to a ruptured aneurysm, which arose from a penetrating artery of the distal middle cerebral artery (MCA; M4 segment). Excision of the aneurysm was successfully achieved via a right pterional approach. The follow-up angiogram demonstrated filling of the parent vessel and no residual aneurysm. This report illustrates the angiographical finding of a penetrating artery aneurysm of the distal MCA and summarizes the previous reports to discuss their pathological and clinical characteristics 20).
 
1) , 4) , 5) , 20)

Ahn JY, Han IB, Joo JY. Aneurysm in the penetrating artery of the distal middle cerebral artery presenting as intracerebral haemorrhage. Acta Neurochir (Wien). 2005 Dec;147(12):1287-90; discussion 1290. Epub 2005 Aug 29. PubMed PMID: 16133768.
2) , 8) , 14)

Lv N, Zhou Y, Yang P, Li Q, Zhao R, Fang Y, Xu Y, Hong B, Zhao W, Liu J, Huang Q. Endovascular treatment of distal middle cerebral artery aneurysms: Report of eight cases and literature review. Interv Neuroradiol. 2016 Feb;22(1):12-7. doi: 10.1177/1591019915617317. Epub 2015 Dec 3. Review. PubMed PMID: 26637241; PubMed Central PMCID: PMC4757379.
3)

Elsharkawy A, Lehečka M, Niemelä M, Billon-Grand R, Lehto H, Kivisaari R, Hernesniemi J. A new, more accurate classification of middle cerebral artery aneurysms: computed tomography angiographic study of 1,009 consecutive cases with 1,309 middle cerebral artery aneurysms. Neurosurgery. 2013 Jul;73(1):94-102; discussion 102. doi: 10.1227/01.neu.0000429842.61213.d5. PubMed PMID: 23615110.
6)

Horiuchi T, Tanaka Y, Takasawa H, Murata T, Yako T, Hongo K. Ruptured distal middle cerebral artery aneurysm. J Neurosurg. 2004;100:384–8.
7)

Lee SM, Park HS, Choi JH, Huh JT. Ruptured mycotic aneurysm of the distal middle cerebral artery manifesting as subacute subduralhematoma. J Cerebrovasc Endovasc Neurosurg. 2013;15:235–40.
9) , 13) , 15) , 16)

Raza SM, Papadimitriou K, Gandhi D, Radvany M, Olivi A, Huang J. Intra-arterial intraoperative computed tomography angiography guided navigation: a new technique for localization of vascular pathology. Neurosurgery. 2012 Dec;71(2 Suppl Operative):ons240-52; discussion ons252. doi: 10.1227/NEU.0b013e3182647a73. PubMed PMID: 22858682.
10) , 11) , 12) , 18)

Ricci A, Di Vitantonio H, De Paulis D, Del Maestro M, Raysi SD, Murrone D, Luzzi S, Galzio RJ. Cortical aneurysms of the middle cerebral artery: A review of the literature. Surg Neurol Int. 2017 Jun 13;8:117. doi: 10.4103/sni.sni_50_17. eCollection 2017. PubMed PMID: 28680736; PubMed Central PMCID: PMC5482160.
17)

Ausman JI, Diaz FG, Malik GM, Tomecek F. A new microsurgical approach to cerebrovascular lesions of the sylvian point: report of two cases. Surg Neurol. 1990 Jul;34(1):48-51. PubMed PMID: 2360163.
19)

Lee SH, Bang JS. Distal Middle Cerebral Artery M4 Aneurysm Surgery Using Navigation-CT Angiography. J Korean Neurosurg Soc. 2007 Dec;42(6):478-80. doi: 10.3340/jkns.2007.42.6.478. Epub 2007 Dec 20. PubMed PMID: 19096593; PubMed Central PMCID: PMC2588183.

Update: Interleukin 6 after aneurysmal subarachnoid hemorrhage

Interleukin 6 after aneurysmal subarachnoid hemorrhage

After rupture of a intracranial aneurysm, high CSF Interleukin 6 levels were found to associate with vasospasm 1) 2) 3).

This aneurysmal subarachnoid hemorrhage (SAH) has been reported to induce an intrathecal inflammatory reaction reflected by cytokine release, particularly interleukin 6 (IL-6), which correlates with early brain damage and poor outcome.

Results provide strong evidence that IL-6 and TNF-α CSF levels are elevated in SAH patients and may participate in SAH development. Thus, these two cytokines could be important biomarkers for early diagnosis and disease monitoring in SAH patients 4).

Higher early IL6 serum levels after aSAH are associated with poor outcome at discharge. In addition, involvement of leukemia inhibitory factor (LIF) in the early inflammatory reaction after aSAH has been demonstrated 5).

CSF IL-6 values of ≥10,000 pg/ml in the early post-SAH period may be a useful diagnostic tool for predicting shunt dependency in patients with acute posthemorrhagic hydrocephalus. The development of shunt-dependent posthemorrhagic hydrocephalus remains a multifactorial process 6).

Case series

2017

The concentrations of serum biomarkers and markers in the CSF were collected in 63 consecutive patients with aSAH and external ventricular drainage. Arithmetical means and standard deviations, area under the curve (AUC), cutoff values (C-OFF), sensitivity (SE), and specificity (SP) were calculated for markers and their correlation with SAHw/o/c, cVSSAH, and VCSAH. RESULTS: Clinical courses included 27 patients with cVSSAH, 17 with VCSAH, and 19 with SAHw/o/c. Mean ± standard deviationCSFIL-6 values were 7588 ± 4580 pg/mL at onset of VCSAH and 4102 ± 4970 pg/mL for cVSSAH and higher than 234 ± 239 pg/mL in SAHw/o/c (P < 0.001). CSFIL-6 showed excellent diagnostic potential for differing between VCSAH and SAHw/o/c (AUC, 1.00; C-OFF, 707; SE, 100%; SP, 100%), and a moderate diagnostic potential for differing VCSAH from cVSSAH (AUC, 0.757; C-OFF, 3100 pg/Ml; SE, 86.7%; SP, 70.6%). The concentration of CSFIL-6 within the cVSSAH group was significantly increased compared with SAHw/o/c (AUC, 0.937; C-OFF, 530 pg/mL; SE, 87.5%; SP, 91.7%).

CSFIL-6 is increased after aSAH in patients with cVSSAH or VCSAH. Patients with a CSFIL-6 level higher than a C-OFF of 3100 pg/mL have an increased likelihood for VCSAH; patients with CSFIL-6 levels between 530 and 3100 pg/mL have an increased posttest probability for cVSSAH 7).

2015

Kao et al. prospectively included 53 consecutive patients treated with platinum coil embolization of the ruptured intracranial aneurysm. Plasma IL-6 levels were measured in the blood samples at the orifices of the aneurysms and from peripheral veins. The outcome measure was the modified Rankin Scale one month after SAH. Multiple logistic regression analyses were used to evaluate the associations between the plasma IL-6 levels and the neurological outcome.

Significant risk factors for the poor outcome were old age, low Glasgow Coma Scale (GCS) on day 0, high Fisher grades, and high aneurysmal and venous IL-6 levels in univariate analyses. Aneurysmal IL-6 levels showed modest to moderate correlations with GCS on day 0, vasospasm grade and Fisher grade. A strong correlation was found between the aneurysmal and the corresponding venous IL-6 levels (ρ = 0.721; P<0.001). In the multiple logistic regression models, the poor 30-day mRS was significantly associated with high aneurysmal IL-6 level (OR, 17.97; 95% CI, 1.51-214.33; P = 0.022) and marginally associated with high venous IL-6 level (OR, 12.71; 95% CI, 0.90-180.35; P = 0.022) after adjusting for dichotomized age, GCS on day 0, and vasospasm and Fisher grades.

The plasma level of IL-6 is an independent prognostic biomarker that could be used to aid in the identification of patients at high-risk of poor neurological outcome after rupture of the intracranial aneurysm 8).


A complete data set (DHEAS and IL-6 serum levels for days 0, 1, 4, 7, 10 and 14 after aSAH) and outcome assessment at discharge according to modified Rankin Scale score (mRS) was available for 53 patients of the initially screened cohort (n = 109). Outcome assessment six months after aSAH was obtained from 41 patients. Logarithmized levels of DHEAS and IL-6 were related to dichotomized functional outcome either assessed at discharge or at six months. A mixed between-within subjects ANOVA was applied for statistical analysis (SPSS 21.0).

DHEAS and IL-6 levels across time were related to functional outcome. Regarding outcome assessment at discharge and at six months after aSAH, DHEAS levels (transformed to square root for statistical purposes) were considerably higher in patients with favorable outcome (mRS 0-2) (p = .001; p = .020). Inversely, in patients with favorable outcome either at discharge or six months after aSAH, lower IL-6 levels (logarithmized for statistical purposes) were observed across time (both p < .001).

Höllig et al. provide new evidence that DHEAS is associated with protective properties resulting in improvement of functional outcome after aSAH, possibly by influencing the inflammatory response after aSAH shown in the decreasing IL-6 serum levels. But the results for outcome six months after SAH are limited due to a high drop-out rate 9).

2011

Daily systemic IL-6 levels were measured in the acute phase in 11 patients with non-aneurysmal perimesencephalic SAH (pmSAH), with bleeding strictly located around the midbrain, and in nine patients with non-aneurysmal non-perimesencephalic (non-pmSAH), with hemorrhage extending into adjacent cisterns (group 1). IL-6 levels were compared with those from patients suffering from aSAH with cerebral vasospasm (CVS) (group 2) and without CVS (group 3). The mean IL-6 level (±standard error of the mean) was significantly lower in group 1 compared to group 2 (9.9±1.9 vs. 29.1±6.7 pg/mL, p=0.018). The difference in mean IL-6 level between group 1 and 3 fell short of significance (9.9±1.9 vs. 14.9±1.1 pg/mL, p=0.073). Patients in group 1 had a significantly better outcome (Glasgow Outcome Scale score 4-5) compared to group 2 (p<0.001) and a trend towards better outcome compared to group 3 (p=0.102). A subgroup analysis revealed a higher mean IL-6 concentration in patients with non-pmSAH compared to patients with pm-SAH (p=0.001). We concluded that systemic IL-6 concentration reflects the severity of the inflammatory stress response and course of the illness. The more benign illness and good prognosis of patients with pmSAH or non-pmSAH in contrast to patients with aSAH is reflected by the lower concentrations of IL-6 10).

2010

A total of 38 consecutive aSAH patients were studied prospectively within 14 days after admission and classified as asymptomatic (n = 9; WFNS grade 1 (1-2), median and quartiles) and symptomatic (n = 29; WFNS grade 4 (2-5)); the latter presenting with acute focal neurological deficits (AFND) (n = 13), delayed cerebral ischemia(DCI). (n = 10) or both (n = 6). Levels of pro-inflammatory cytokine IL-6 were determined in cerebral extracellular fluid (ECF, using cerebral microdialysis), cerebrospinal fluid (CSF) and plasma for 10 days after aSAH. Additionally, C-reactive protein (CRP) levels were measured in plasma.

High IL-6 levels in CSF, ECF and plasma were found in all patients, reflecting a pronounced local inflammatory response after aSAH, followed only in symptomatic patients by a delayed systemic inflammation (CRP P < 0.025, days 7-9 after aSAH). In all compartments, IL-6 levels appeared to be higher in symptomatic patients, accompanied also by a higher ECF lactate-pyruvate ratio (P = 0.04). Cerebral, but not plasma IL-6, levels were indicative of the development of DCI in symptomatic patients (ECF P = 0.003; CSF P = 0.001).

A pronounced initial cerebral inflammatory state was observed in patients of all WFNS grades, suggesting that IL-6 elevations are not necessarily detrimental. Cerebral, but not plasma IL-6, levels were predictive of the development of delayed ischemic deficits in symptomatic patients, suggesting that CSF or ECF are the best sampling media for future studies 11).

Ďuriš K, Neuman E, Vybíhal V, Juráň V, Gottwaldová J, Kýr M, Vašků A, Smrčka M. Early Dynamics of Interleukin-6 in Cerebrospinal Fluid after Aneurysmal Subarachnoid Hemorrhage. J Neurol Surg A Cent Eur Neurosurg. 2017 Sep 4. doi: 10.1055/s-0037-1604084. [Epub ahead of print] PubMed PMID: 28869993.

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Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schutt S, et al. Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry. 2001;70: 534–537.
2)

Hendryk S, Jarzab B, Josko J. Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH. Neuro Endocrinol Lett. 2004;25: 141–147.
3)

Schoch B, Regel JP, Wichert M, Gasser T, Volbracht L, Stolke D. Analysis of intrathecal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage. Neurosurgery. 2007;60: 828–836; discussion 828–836.
4)

Wu W, Guan Y, Zhao G, Fu XJ, Guo TZ, Liu YT, Ren XL, Wang W, Liu HR, Li YQ. Elevated IL-6 and TNF-α Levels in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients. Mol Neurobiol. 2015 Jun 11. [Epub ahead of print] PubMed PMID: 26063595.
5)

Höllig A, Remmel D, Stoffel-Wagner B, Schubert GA, Coburn M, Clusmann H. Association of early inflammatory parameters after subarachnoid hemorrhage with functional outcome: A prospective cohort study. Clin Neurol Neurosurg. 2015 Aug 28;138:177-183. doi: 10.1016/j.clineuro.2015.08.030. [Epub ahead of print] PubMed PMID: 26355810.
6)

Wostrack M, Reeb T, Martin J, Kehl V, Shiban E, Preuss A, Ringel F, Meyer B, Ryang YM. Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage: The Role of Intrathecal Interleukin-6. Neurocrit Care. 2014 May 20. [Epub ahead of print] PubMed PMID: 24840896.
7)

Lenski M, Huge V, Briegel J, Tonn JC, Schichor C, Thon N. Interleukin 6 in the Cerebrospinal Fluid as a Biomarker for Onset of Vasospasm and Ventriculitis After Severe Subarachnoid Hemorrhage. World Neurosurg. 2017 Mar;99:132-139. doi: 10.1016/j.wneu.2016.11.131. Epub 2016 Dec 5. PubMed PMID: 27931942.
8)

Kao HW, Lee KW, Kuo CL, Huang CS, Tseng WM, Liu CS, Lin CP. Interleukin-6 as a Prognostic Biomarker in Ruptured Intracranial Aneurysms. PLoS One. 2015 Jul 15;10(7):e0132115. doi: 10.1371/journal.pone.0132115. eCollection 2015. PubMed PMID: 26176774; PubMed Central PMCID: PMC4503596.
9)

Höllig A, Thiel M, Stoffel-Wagner B, Coburn M, Clusmann H. Neuroprotective properties of dehydroepiandrosterone-sulfate and its relationship to interleukin 6 after aneurysmal subarachnoid hemorrhage: a prospective cohort study. Crit Care. 2015 May 21;19:231. doi: 10.1186/s13054-015-0954-1. PubMed PMID: 25993987; PubMed Central PMCID: PMC4462180.
10)

Muroi C, Bellut D, Coluccia D, Mink S, Fujioka M, Keller E. Systemic interleukin-6 concentrations in patients with perimesencephalic non-aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2011 Dec;18(12):1626-9. doi: 10.1016/j.jocn.2011.03.022. Epub 2011 Oct 22. PubMed PMID: 22019436.
11)

Sarrafzadeh A, Schlenk F, Gericke C, Vajkoczy P. Relevance of cerebral interleukin-6 after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2010 Dec;13(3):339-46. doi: 10.1007/s12028-010-9432-4. PubMed PMID: 20725805.