Category Archives: Vascular

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.

4) , 12)

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.

5)

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.

7) , 16)

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.

4th Annual EANS Vascular Section Meeting and Joint EANS/ESMINT Meeting

4th Annual EANS Vascular Section Meeting and Joint EANS/ESMINT Meeting

September 7 — September 8

Nice, France

 

Topics for abstracts can include (but are not limited to):
Vascular malformations
Vascular rare diseases
Experimental vascular neurosurgery
Treatment and prevention of ischemia
Aneurysms
Management of Subarachnoid Haemorrhage

Please visit the meeting website here.

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.

1)

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.

Update: Internal carotid artery bifurcation aneurysm

Internal carotid artery bifurcation aneurysm

Internal carotid artery bifurcation aneurysms are subtype of internal carotid artery aneurysm.

Epidemiology

Internal carotid artery bifurcation aneurysms represent between 2.4% and 4% of all intracranial aneurysm1) 2)3) 4).

Complications

They frequently rupture at a younger age compared to other intracranial aneurysms 5).

Additionally, the increased hemodynamic stress at this level translates into a higher rate of recurrence compared with aneurysms in other locations6) 7)

Classification

Small

Large

Giant

Projection

Superior

Anterior

Posterior

Treatment

Treatment is therefore recommended since they tend to bleed at a lower age than other aneurysms 8).

The presence of multiple perforators in this area along with the angle of origin often skewed toward the MCA or the anterior cerebral artery primarily can make treatment challenging 9).

Surgical treatment

The surgical treatment of ICA bifurcation aneurysms is particularly challenging, due to their location at the highest point of the ICA and the presence of multiple perforators at this level that may be adherent to the back side of the aneurysm 10)

Endovascular treatment

Endovascular treatment of ICA bifurcation aneurysms is feasible and effective and is associated with high immediate angiographic occlusion rates. However, retreatment rates and procedure-related morbidity and mortality are non-negligible 11).

Periprocedural complications following endovascular treatment of ICA terminus aneurysms are not negligible. Aneurysms at this location are at a high risk of ischemic stroke in the territory of the ipsilateral MCA (either from distal emboli during the procedure or clot formation at the level of the neck with impairment of distal MCA flow), a potential source of serious morbidity and mortality 12) 13) 14).

In the meta-analysis of Morales-Valero et al., perioperative morbidity rates were approximately 4% and mortality rates were 3%. Perioperative stroke was a major contributor to morbidity and mortality, occurring in approximately 3% of patients. Although good long-term neurologic outcome was achieved in 90% of patients regardless of aneurysm rupture status, the periprocedural complication rate reported is not trivial. Particularly worrisome is the procedure-related mortality of 4% for unruptured and 6% for ruptured ICA bifurcation aneurysms. These findings stress the importance of proper patient selection because these aneurysms are often adequately and effectively treatable with surgical clip ligation. The high retreatment rate observed in the meta-analysis and in the own series is similar to that reported for aneurysms located in other bifurcation points 15).

Videos

Case series

2016

Fifty-nine patients with 61 unruptured ICAbifAs were included. Seven aneurysms were treated surgically (11.5 %), 22 underwent endovascular treatment (36 %), and 32 were managed conservatively (52.5 %). In the surgical group, short- and long-term complete aneurysm occlusion rates were 100 % with no cases of perioperative or long-term permanent morbidity or treatment-related mortality. In the endovascular group, two patients (11.7 %) with giant aneurysms had perioperative thromboembolic events with transient morbidity. There was one case of aneurysm rupture at follow-up in a giant aneurysm treated with partial coil embolization. Complete/near-complete occlusion rates were 63 %. There was one case of aneurysm rupture after 114 aneurysm-years of follow-up in the conservative management group (0.89 %/year), but no ruptures were observed in small aneurysms selected for conservative management.

Unruptured small ICAbifAs have a benign natural history. In patients selected for treatment, excellent results can be achieved in the vast majority of patients with judicious use of endovascular and surgical therapy 16).

2015

A total of 58 patients with ICA bifurcation aneurysms were treated. By interdisciplinary consensus, 30 aneurysms were assigned for coiling and 28 for clipping. Patients who underwent surgical clipping were younger and had larger aneurysms. More patients were assigned to coiling if their aneurysms originated only from the ICA bifurcation or projected superiorly. For the combined angiographic endpoint, complete and nearly complete occlusion (Raymond-Roy I + II), similar rates of 96% (coiling) or 100% (clipping) could be achieved. Raymond-Roy I occlusion occurred more often after clipping (79% vs 41% coiling). Follow-up of the endovascular group showed minor recanalization of the aneurysm neck (Raymond-Roy II) in 42%. One patient (4%) showed a major recanalization (Raymond-Roy III) and needed re-treatment. For incidental findings, no bleeding complications or new persistent neurological deficits occurred during follow-up.

Treatment of ICA bifurcation aneurysms after interdisciplinary assignment to clipping or coiling is effective and safe. Despite significantly more minor recanalizations after coiling, the re-treatment rate was very low, and no bleeding was observed during follow-up. Multivariate analysis revealed that origin only from the ICA bifurcation was an independent predictor of aneurysm recanalization after endovascular treatment 17).

2007

Internal carotid artery (ICA) bifurcation aneurysms are relatively uncommon and frequently rupture at a younger age compared to other intracranial aneurysms.

Gupta et al treated a total of 999 patients for intracranial aneurysms, of whom 89 (8.9%) had ICA bifurcation aneurysms, and 42 of the 89 patients were 30 years of age or younger. The study analyzed the clinical records of 70 patients with ICA bifurcation aneurysms treated from mid 1997 to mid 2003. Multiple aneurysms were present in 15 patients. Digital subtraction angiography films were studied in 55 patients to identify vasospasm and aneurysm projection. The aneurysm projected superiorly in most of these patients (37/55, 67.3%).

They preferred to minimize frontal lobe retraction, so widely opened the sylvian fissure to approach the ICA bifurcation and aneurysm neck. Elective temporary clipping was employed before the final dissection and permanent clip application. Vasospasm was present in 24 (43.6%) of 55 patients. Forty-eight (68.6%) of the 70 patients had good outcome, 14 (20%) had poor outcome, and eight (11.4%) died. Patients with ICA bifurcation aneurysms tend to bleed at a much younger age compared to those with other intracranial aneurysms. Wide opening of the sylvian fissure and elective temporary clipping of the ICA reduces the risk of intraoperative rupture and perforator injury. Mortality was mainly due to poor clinical grade and intraoperative premature aneurysm rupture 18).

2002

A series of 25 patients treated by clipping under the operating microscope are analyzed and compared with previous cases. Twenty-five patients, 11 men and 14 women (mean age 51 years), were treated by the same neurosurgeon. Seventeen patients presented with subarachnoid hemorrhage (Hunt & Kosnik Grade I in three, II in five, III in two, IV in seven), five with unruptured ICA bifurcation aneurysms, and three with unruptured ICA bifurcation aneurysms but another ruptured aneurysm. There were 23 small, one large, and one giant ICA bifurcation aneurysms. The projection was superior in 12, anterior in seven, and posterior in six cases. Pterional approach was employed for all cases. Outcomes were evaluated at discharge with the Glasgow Outcome Scale. Favorable outcomes (good recovery (GR) and moderate disability (MD)) were obtained in ten of 17 patients with ruptured ICA bifurcation aneurysm. Favorable outcomes were significantly greater in Grades I and II (three in I, four in II) than in Grades III and IV (one in III, two in IV; P=0.0498). Seven of eight patients with unruptured ICA bifurcation aneurysm had favorable outcomes. Temporary clipping and projection of the aneurysm did not affect the outcome. Causative factors of unfavorable outcomes were primary brain damage in cases of small and large aneurysms and perforator damage in the case of giant aneurysm. Poor clinical grade and vasospasm are the causative factors of poor outcome in patients with ruptured ICA bifurcation aneurysm. Preservation of perforators is crucial in cases of giant aneurysm. Clipping of unruptured ICA bifurcation aneurysms is recommended since they tend to bleed at a lower age than other aneurysms 19).

Case reports

2015

A 70-year-old man with progressive visual disturbances, left superior quadrantanopsia, and right-sided papilledema underwent imaging that demonstrated a right internal carotid artery (ICA) terminus aneurysm with third-ventricle mass effect and ipsilateral optic nerve and chiasm compression. We performed a right modified orbitozygomatic craniotomy, with proximal control and dissection of the aneurysm and small perforator arteries. Temporary ICA and anterior cerebral artery (ACA) clips allowed placement of a large curved permanent clip, reconstructing the ICA bifurcation and maintaining adequate patency of the ACA and middle cerebral artery. Complete aneurysm obliteration was confirmed by intraoperative indocyanine green angiography and postoperative CT angiography. The video can be found here: http://youtu.be/5WEEgmA-g2A20).


A 64-year-old woman, with visual deficit, harboring a large wide-necked aneurysm located at the junction between left internal carotid artery and left A1 segment of anterior cerebral artery, was submitted to endovascular treatment. As she had pre-existing occlusion of left internal carotid, approach from the contralateral internal carotid was used to advance the pipeline embolization device through the anterior communicating artery and place the flow diverter horizontally across the neck (from M1 to A1). Coil embolization was also performed through a microcatheter navigated via posterior communicating artery. The intervention was uneventful, with total aneurysm occlusion. Patient presented with visual improvement on follow-up.

Horizontal deployment of pipeline embolization device appears to be an acceptable and feasible alternative to treat internal carotid bifurcation aneurysms. Long-term follow-up and a greater number of cases are mandatory to establish the safety of this strategy 21).

2009

A surgical case of an eleven year old boy with excellent outcome is reported, with a subsequent review on the subject. Patients may present with classical subarachnoidal hemorrhage, but also with compressive signs with bigger and unruptured lesions. Initial management of these cases is basically the same of older patients, considering their age, weight and special intensive care for infants 22).

2006

A 58-year-old hypertensive woman presenting with mild headaches underwent computed tomography, which showed a nonruptured aneurysm of the left internal carotid artery. She subsequently underwent cerebral angiography, confirming that the aneurysm was located at the left terminal carotid segment with a wide neck. INTERVENTION: Using a cross-over approach from the contralateral internal carotid artery, a new self-expandable stent was advanced through the anterior communicating artery and placed horizontally across the aneurysm neck. Aneurysm occlusion was performed by subsequent trans-stent catheterization of the aneurysm and coil packing.

Successful stent placement allowed subtotal coil occlusion of the aneurysm with a good anatomic and clinical result. No complications were encountered. The new self-expandable stent is a highly flexible, low-profile device that can be safely navigated through tortuous intracranial vessels even in a crossover technique. Its radial force and closed cell design is suitable for stent-assisted coiling and may be superior to stents with an open cell design 23).

1)

Sakamoto S, Ohba S, Shibukawa M, et al. Characteristics of aneurysms of the internal carotid artery bifurcation. Acta Neurochir (Wien) 2006;148:139 –43, discussion 143
2) , 8) , 9) , 19)

Miyazawa N, Nukui H, Horikoshi T, Yagishita T, Sugita M, Kanemaru K. Surgical management of aneurysms of the bifurcation of the internal carotid artery. Clin Neurol Neurosurg. 2002 May;104(2):103-14. PubMed PMID: 11932039.
3) , 10)

Lehecka M, Dashti R, Romani R, et al. Microneurosurgical management of internal carotid artery bifurcation aneurysms. Surg Neurol 2009;71:649 –67
4) , 6) , 12)

van Rooij WJ, Sluzewski M, Beute GN. Internal carotid bifurcation aneurysms: frequency, angiographic anatomy and results of coiling in 50 aneurysms. Neuroradiology 2008;50:583–87
5) , 18)

Gupta SK, Khosla VK, Chhabra R, Mohindra S, Bapuraj JR, Khandelwal N, Mukherjee KK, Tewari MK, Pathak A, Mathuriya SN. Internal carotid artery bifurcation aneurysms: surgical experience. Neurol Med Chir (Tokyo). 2007 Apr;47(4):153-7; discussion 157-8. PubMed PMID: 17457018.
7)

Ingebrigtsen T, Morgan MK, Faulder K, et al. Bifurcation geometry and the presence of cerebral artery aneurysms. J Neurosurg 2004;101:108 –13
11) , 15)

Morales-Valero SF, Brinjikji W, Murad MH, Wald JT, Lanzino G. Endovascular treatment of internal carotid artery bifurcation aneurysms: a single-center experience and a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2014 Oct;35(10):1948-53. doi: 10.3174/ajnr.A3992. Epub 2014 Jun 5. Review. PubMed PMID: 24904050.
13)

Uemura A, Musacchio M, Cardoso M, et al. Internal carotid bifurcation aneurysms: anatomical features and outcome of endovascular treatment. Neuroradiol J 2008;21:574 –78
14)

Oishi H, Yamamoto M, Nonaka S, et al. Endovascular therapy of internal carotid artery bifurcation aneurysms. J Neurointerv Surg 2013;5:400 –04
16)

La Pira B, Brinjikji W, Burrows AM, Cloft HJ, Vine RL, Lanzino G. Unruptured internal carotid artery bifurcation aneurysms: general features and overall results after modern treatment. Acta Neurochir (Wien). 2016 Nov;158(11):2053-2059. PubMed PMID: 27644699.
17)

Konczalla J, Platz J, Brawanski N, Güresir E, Lescher S, Senft C, du Mesnil de Rochemont R, Berkefeld J, Seifert V. Endovascular and surgical treatment of internal carotid bifurcation aneurysms: comparison of results, outcome, and mid-term follow-up. Neurosurgery. 2015 May;76(5):540-50; discussion 550-1. doi: 10.1227/NEU.0000000000000672. PubMed PMID: 25635884.
20)

Rangel-Castilla L, Spetzler RF. Microsurgical management of a large ICA bifurcation aneurysm. Neurosurg Focus. 2015 Jul;39 Video Suppl 1:V18. doi: 10.3171/2015.7.FocusVid.14646. PubMed PMID: 26132616.
21)

Trivelato FP, Araújo JF, Salles Rezende MT, Ulhôa AC. A Novel Configuration of Pipeline Embolization Device for Internal Carotid Bifurcation Region Aneurysms: Horizontal Deployment. Clin Neuroradiol. 2015 Jun 6. [Epub ahead of print] PubMed PMID: 26047919.
22)

Meireles Borba A, Santana Pereira RS, Godinho A, Casulari LA. Internal carotid bifurcation aneurysm in childhood: a case report and literature review. J Neurosurg Sci. 2009 Sep;53(3):131-6. Review. PubMed PMID: 20075826.
23)

Benndorf G, Klucznik RP, Meyer D, Strother CM, Mawad ME. “Cross-over” technique for horizontal stenting of an internal carotid bifurcation aneurysm using a new self-expandable stent: technical case report. Neurosurgery. 2006 Feb;58(1 Suppl):ONS-E172; discussion ONS-E172. PubMed PMID: 16462622.

Update: Chronic subdural hematoma recurrence

Chronic subdural hematoma recurrence

Epidemiology

Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques twist drill craniostomy (TDC), burr hole craniostomy, craniotomy range from 5% to 30%. 1)

Risk factors

Chon et al. shown that postoperative midline shifting (≥5 mm), diabetes mellitus, preoperative seizure, preoperative width of hematoma (≥20 mm), and anticoagulant therapy were independent predictors of the recurrence of chronic subdural hematoma. According to internal architecture of hematoma, the rate of recurrence was significantly lower in the homogeneous and the trabecular type than the laminar and separated type 2).

The recurrence rate of chronic subdural hematoma cSDH seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the hematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2 (COX-2).


Antiplatelet therapy

Antiplatelet therapy significantly influences the recurrence of CSDH 3).

Pneumocephalus

Remaining pneumocephalus is seen as an approved factor of recurrence 4) 5).

Septation

Jack et al.found a 12% reoperation rate. CSDH septation (seen on computed tomogram scan) was found to be an independent risk factor for recurrence requiring reoperation (p=0.04). Larger post-operative subdural haematoma volume was also significantly associated with requiring a second drainage procedure (p<0.001). Independent risk factors of larger post-operative haematoma volume included septations within a CSDH (p<0.01), increased pre-operative haematoma volume (p<0.01), and a greater amount of parenchymal atrophy (p=0.04). A simple scoring system for quantifying recurrence risk was created and validated based on patient age (< or ≥80 years), haematoma volume (< or ≥160cc), and presence of septations within the subdural collection (yes or no).

Septations within CSDHs are associated with larger post-operative residual haematoma collections requiring repeat drainage. When septations are clearly visible within a CSDH, craniotomy might be more suitable as a primary procedure as it allows greater access to a septated subdural collection. The proposed scoring system combining haematoma volume, age, and presence of septations might be useful in identifying patients at higher risk for recurrence 6).

Membranectomy

Opening the internal hematoma membrane does not alter the rate of patients requiring revision surgery and the number of patients showing a marked residual hematoma six weeks after evacuation of a CSDH 7).

In the study of Lee et al, an extended surgical approach with partial membranectomy has no advantages regarding the rate of reoperation and the outcome. As initial treatment, burr-hole drainage with irrigation of the hematoma cavity and closed-system drainage is recommended. Extended craniotomy with membranectomy is now reserved for instances of acute rebleeding with solid hematoma 8).

Diabetes

Surgeons should consider informing patients with diabetes mellitus that this comorbidity is associated with an increased likelihood of recurrence

9) 10) 11).


Balser et al. report 11% recurrence, which included individuals who recurred as late as 3 years after initial diagnosis 12).

Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the ‘self-resolution’ period can be used as significantly radiological predictors of recurrence 13).

A structural equation model showed a significant association between increased antiinflammatory activity in hematoma fluid samples and a lower risk of recurrence, but this relationship was not statistically significant in venous blood samples. Moreover, these findings indicate that anti-inflammatory activities in the hematoma may play a role in the risk of a recurrence of CSDH 14).

Irrigation with artificial cerebrospinal fluid (ACF) decreased the rate of CSDH recurrence 15).

Treatment

There is no definite operative procedure for patients with intractable chronic subdural hematoma (CSDH).

Most recurrent hematomas are managed successfully with burr hole craniostomies with postoperative closed-system drainage. Refractory hematomas may be managed with a variety of techniques, including craniotomy or subdural-peritoneal shunt placement 16).

Although many studies have reported risk factors or treatments in efforts to prevent recurrence, those have focused on single recurrence, and little cumulative data is available to analyze refractory CSDH.

Matsumoto et al. defined refractory CSDH as ≥2 recurrences, then analyzed and compared clinical factors between patients with single recurrence and those with refractory CSDH in a cohort study, to clarify whether patients with refractory CSDH experience different or more risk factors than patients with single recurrence, and whether burr-hole irrigation with closed-system drainage reduces refractory CSDH.

Seventy-five patients had at least one recurrence, with single recurrence in 62 patients and ≥2 recurrences in 13 patients. In comparing clinical characteristics, patients with refractory CSDH were significantly younger (P=0.04) and showed shorter interval to first recurrence (P<0.001). Organized CSDH was also significantly associated with refractory CSDH (P=0.02). Multivariate logistic regression analysis identified first recurrence interval <1 month (OR 6.66, P<0.001) and age <71 years (OR 4.16, P<0.001) as independent risk factors for refractory CSDH. On the other hand, burr-hole irrigation with closed-system drainage did not reduce refractory CSDH.

When patients with risk factors for refractory CSDH experience recurrence, alternative surgical procedures may be considered as the second surgery, because burr-hole irrigation with closed-system drainage did not reduce refractory CSDH 17).

Implantation of a reservoir 18) 19) 20).

Subdural-peritoneal shunt 21).

Middle meningeal artery embolization

Embolization of the MMA is effective for refractory CSDH or CSDH patients with a risk of recurrence, and is considered an effective therapeutic method to stop hematoma enlargement and promote resolution 22) 23) 24) 25) 26) 27).

A pilot study indicated that perioperative middle meningeal artery (MMA) embolization could be offered as the least invasive and most effectual means of treatment for resistant patients of CSDHs with 1 or more recurrences 28).

Chihara et al. have treated three cases of CSDH with MMA embolization to date, but there was a postoperative recurrence in one patient, which required a craniotomy for hematoma removal and capsulectomy. MMA embolization blocks the blood supply from the dura to the hematoma outer membrane in order to prevent recurrences of refractory CSDH. Histopathologic examination of the outer membrane of the hematoma excised during craniotomy showed foreign-body giant cells and neovascular proliferation associated with embolization. Because part of the hematoma was organized in this case, the CSDH did not resolve when the MMA was occluded, and the development of new collateral pathways in the hematoma outer membrane probably contributed to the recurrence. Therefore, in CSDH with some organized hematoma, MMA embolization may not be effective. Magnetic resonance imaging (MRI) should be performed in these patients before embolization 29).

Case series

2016

Chronic subdural hematomas (cSDHs) have shown an increasing incidence in an ageing population over the last 20 years, while unacceptable recurrence rates of up to 30 % persist. The chronic subdural hematoma recurrence rate seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the haematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2 (COX 2). With this investigator-initiated trial (IIT) it was thought to diminish the recurrence rate of operated-on cSDHs by administering a selective COX-2 inhibitor (Celecoxib) over 4 weeks’ time postoperatively in comparison to a control group.

The thesis of risk reduction of cSDH recurrence in COX-2-inhibited patients was to be determined in a prospective, randomised, two-armed, open phase-II/III study with inclusion of 180 patients over a 2-year time period in four German university hospitals. The treated- and untreated-patient data were to be analysed by Fisher’s exact test (significance level of alpha, 0.05 [two-sided]).

After screening of 246 patients from January 2009 to April 2010, the study had to be terminated prematurely as only 23 patients (9.3 %) could be enrolled because of on-going non-steroid anti-rheumatic (NSAR) drug treatment or contraindication to Celecoxib medication. In the study population, 13 patients were treated in the control group (six women, seven men; average age 66.8 years; one adverse event (AE)/serious adverse event (SAE) needing one re-operation because of progressive cSDH (7.7 %); ten patients were treated in the treatment group (one woman, nine men; average age 64.7 years; five AEs/SAEs needing two re-operations because of one progressive cSDH and one wound infection [20 %]). Significance levels are obsolete because of insufficient patient numbers.

The theoretical advantage of COX-2 inhibition in the recurrent cSDH could not be transferred into the treatment of German cSDH patients as 66.6 % of the patients showed strict contraindications for Celecoxib. Furthermore, 55 % of the patients were already treated with some kind of COX-2 inhibition and, nevertheless, developed cSDH. Thus, although conceptually appealing, an anti-angiogenic therapy with COX-2 inhibitors for cSDH could not be realised in this patient population due to the high prevalence of comorbidities excluding the administration of COX2 inhibitors 30).

2010

Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques twist drill craniostomy (TDC), burr holecraniostomy, craniotomy range from 5% to 30%. Use of drain has improved recurrence rates when used with burr-hole craniostomy. Now, we analyze predictors of recurrence of TDC with drain.

Three hundred twelve consecutive patients with CSDH have been studied in a retrospective study. Operative technique in all patients consisted in TDC with drain. Data recorded included any associated comorbidity. Radiologic measures of the CSDH before and after the procedure were studied. Clinical evaluation included Modified Rankin Scale, Glasgow Coma Scale (GCS), and neurological deficits. Two groups were compared: recurrence group and nonrecurrence group. Follow-up was for at least 1 year.

Twelve percent experienced recurrence. Preoperative CSDH width, preoperative midline shift, postoperative midline width, postoperative CSDH width, and residual CSDH 1 month later were significantly associated with CSDH recurrence. The logistic regression model for the multivariate analysis revealed that postoperative midline shift and postoperative neurological deficit were significantly associated with CSDH recurrence. The duration of treatment with dexamethasone was found not to be related with recurrence. Mortality before hospital discharge was 1%. Hospital stay was 2.5 days.

TDC with drain has similar results in recurrence rates, morbidity, mortality, and outcome as other techniques as burr-hole craniostomy with drain. Preoperative and postoperative hematoma width and midline shift are independent predictors of recurrence. Brain re-expansion and time of drain maintenance are important factors related with recurrence of CSDH. Future CSDH reservoirs must avoid negative pressure and sudden pressure changes inside the whole closed drain system 31).

Case reports

2016

Mewada et al. report a case with right hemiparesis and aphasia 1 month after a fall from a bicycle. Computed tomography scan of the head showed left chronic subdural hematoma, which was evacuated by burr-hole drainage. The postoperative course was complicated by reaccumulation within short period of time. On superselective digital subtraction angiography of MMA, iatrogenic dAVF was found on left side. We embolized successfully it using n-butyl cyanoacrylate after a third irrigation. No reaccumulation found in the postoperative period or at last follow-up. They proposed a treatment protocol based on the own experience and literature review.

Refractory chronic subdural hematoma with reaccumulation within a short interval should be subjected to digital subtraction angiography of the MMA. Embolization of ipsilateral MMA is safe, effective, and a useful option for the treatment of iatrogenic dAVF and resolution of hematoma 32).


An 85-year-old male presented with left CSDH, which recurred five times. The hematoma was irrigated and drained through a left frontal burr hole during the first to third surgery and through a left parietal burr hole during the fourth and fifth surgery. The hematoma had no septation and was well-evacuated during each surgery. Antiplatelet therapy for preventing ischemic heart disease was stopped after the second surgery, the hematoma cavity was irrigated with artificial cerebrospinal fluid at the third surgery, and the direction of the drainage tube was changed to reduce the postoperative subdural air collection at the fourth surgery. However, none of these interventions was effective. He was successfully treated by fibrin glue injection into the hematoma cavity after the fifth surgery.

This procedure may be effective for refractory CSDH in elderly patients 33).


A 67-year-old man with dural arteriovenous fistula (AVF) presenting as a non-traumatic chronic subdural hematoma (CSDH). This previously healthy patient was hospitalized due to progressive headache with subacute onset. He underwent burr-hole surgery twice for evacuating the left CSDH that was thickest at the posterior temporal area. The operative procedure and finding was not extraordinary, but subdural hematoma slowly progressed for days following the revision surgery. After investigation by super-selective external carotid angiography, a dural AVF found near the transverse-sigmoid sinus was diagnosed. Dural AVF was completely occluded with trans-arterial injecting polyvinyl alchol particles into the petrosquamosal branch of the middle meningeal artery. The patient showed a good neurological outcome with no additional intervention. Brain surgeons have to consider the possibility of dural AVF and perform cerebral angiogram if necessary when they manage the cases that have a spontaneously occurred and repeatedly recurring CSDH 34).

2007

Spontaneous intracranial hypotension (SIH) is reported to cause chronic subdural hematoma (SDH), however diagnosis of SIH in patients with SDH is not always easy.

Takahashi et al. report a case of chronic SDH refractory to repeated drainage, which was attributed to SIH. A forty-five-year-old man who had been suffering from orthostatic headache for one month was admitted to our hospital presenting with unconsciousness and hemiparesis. CT on admission revealed a chronic subdural hematoma, which was successfully treated once with subdural drainage. However, the patient fell into unconscious again with recurrence of the hematoma within several days. After two more sessions of drainage, SIH due to cerebrospinal fluid leakage was diagnosed with spinal magnetic resonance imaging (MRI) and radionuclide cisternography. Spinal MRI demonstrated abnormal fluid accumulation in the thoracic epidural space, and the radionuclide cisternogram showed early excretion of tracer into urine as well as absence of intracranial tracer filling. After treatment with epidural blood patching, the hematoma rapidly disappeared and he was discharged without symptoms. In the treatment of chronic SDH, especially in young to middle aged patient without preceding trauma or hematological disorders, physicians should pay attention to underlying SIH to avoid multiple surgery. MRI of the spine as well as radionuclide cisternography is useful in evaluation of this condition 35).

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