5th ANNUAL EANS VASCULAR SECTION MEETING

7 – 8 SEPTEMBER 2018

NICE, FRANCE

http://vascular.squarespace.com/

The meeting is being held in conjunction with the annual ESMINT Congress.  A joint EANS/ESMINT session, also featuring a number of prominent speakers from both Europe and the US, will be organized again and we encourage as many as possible of you to support and attend this joint meeting as well.

The EANS Vascular Section Meeting provides an interdisciplinary platform for neurosurgeons, neurointerventionalists, neuroradiologists, neurologists, and others who are interested in the treatment of cerebrovascular diseases.

UpToDate: Decompressive craniectomy for intracerebral hemorrhage

Decompressive craniectomy for intracerebral hemorrhage

Systematic review

Yao et al. conducted a systematic review to verify the effects of decompressive craniectomy (DC) on improving outcome in spontaneous intracerebral hemorrhage.

Through searching several electronic databases, they screened eligible publications. Respective risk ratio (RR) and its 95% confidence interval (CI) were calculated, data were synthesized with a fixed-effect model, and sensitivity analyses and subgroup analyses were performed. Publication bias was measured with Begg and Egger tests.

Overall effect showed that DC significantly reduced the poor outcome compared with the control group (RR, 0.91; 95% CI, 0.84-0.99; P = 0.03). But in the subgroup analyses, only studies published after 2010, studies using hematoma evacuation as control, and studies measuring outcome with Glasgow outcome score showed better outcomes in the DC group than in the control group. The other subgroup analyses and sensitivity analyses achieved inconsistent results. Compared with the control group, DC effectively decreased mortality (RR, 0.67; 95% CI, 0.53-0.85; P = 0.0008). The sensitivity analyses and subgroup analyses achieved consistent results.

The application of DC effectively reduced mortality in patients with sICH. DC might improve functional outcomes in certain populations and needs further verification. DC is not associated with increased incidences of postoperative rebleeding and hydrocephalus 1).

Experimental work

Marinkovic et al. from Helsinki, Finland, used the model of autologous blood injection into the basal ganglia in rats. After induction of ICH and then magnetic resonance imaging, animals were randomly allocated to groups representing no craniectomy (n = 10) or to craniectomy at 1, 6, or 24 hours. A fifth group without ICH underwent craniectomy only. Neurological and behavioral outcomes were assessed on days 1, 3, and 7 after ICH induction. Furthermore, terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells were counted.

After 7 days, compared with the ICH + no craniectomy group, all craniectomy groups had strikingly lower mortality (P < 0.01), much better neurological outcome (P < 0.001), and more favorable behavioral outcome. A trend occurred in the ICH + no craniectomy group toward more robust apoptosis.

Decompressive craniectomy performed up to 24 hours improved outcome after experimental ICH, with earlier intervention of greater benefit 2).

Case series

Rasras et al. from the Department of Neurosurgery, Ahvaz Jundishapur University of Medical Sciences, AhvazIran, sought to assess the preliminary utility of decompressive hemicraniectomy (DHC) without clot evacuation in patients with deep-seated supratentorial ICH.

Patients with deep seated spontaneous intracerebral hemorrhage who were admitted to the Golestan Hospital, of Ahvaz, from November 2014 to February 2016, were prospectively enrolled in a study. A prospective clinical trial where 30 patients diagnosed having large hypertensive ICH was randomly allocated to either group A or B using permuted-block randomization. These patients (n = 30), who all had large deep seated supratentorial ICH with surgery indications, were randomly divided to two groups. ultimately, in one group (n = 13), large DHC was performed without clot evacuation, while in the other (n = 17), craniotomy with clot evacuation was done. Data pertaining to the patients characteristics and treatment outcomes were prospectively collected.

There was no statistically significant difference between two treatment groups (P > 0.05). No significant difference was observed between the two groups in terms of mortality and GOS at 6 months (P > 0.05); nevertheless, the good outcome (Glasgow Outcome Scale = 4-5) for patients with hematoma evacuation was slightly higher (35.3%) as compared to the DHC patients without clot evacuation (30.7%).

Decompresive craniectomy without clot evacuation in deep seated ICH can be accomplished with identical mortality and outcome in comparison to patient that undergone clot evacuation 3).


A total of 54 eligible patients with spontaneous supratentorial hemorrhage (median age, 55 years; interquartile range, 47-64 years) who underwent decompressive craniectomy were retrospectively matched to 72 patients managed with best medical treatment (median age, 58 years; interquartile range, 32-74 years). Glasgow Outcome Scale (GOS) scores were dichotomized into favorable and unfavorable outcomes. Survival and functional outcomes were analyzed at discharge, 3, 6, and 12 months.

Survival in the craniectomy group was significantly higher compared with the medical treatment group at 30 days, 6, and 12 months (76%, 70%, and 70% vs. 60%, 57%, and 52% respectively; all P ≤ 0.05). There was no difference in functional outcomes at discharge, 3, 6, or 12 months after hemorrhage (all P > 0.05). Decompressive craniectomy was associated with longer hospital stay (median of 30 days vs. 7 days in the control group; P < 0.001). Hospital adverse events were more frequent in the craniectomy group than in the control group (76% vs. 33%; P < 0.001), the commonest adverse events being pneumonia and urinary tract infections.

They showed that decompressive craniectomy significantly improved survival compared with medical treatment with lasting benefits. This improvement came at a cost of increased length of hospital stay and related adverse events. There was no improvement in functional outcome 4).


Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift 5).


Of 21 patients who underwent DC for hemispheric hypertensive ICH in the Department of Neurosurgery, National Defense Medical College, Tokorozawa, Saitama, Japan, eleven of the patients were male and 10 were female, with an age range of 22-75 years (mean, 56.6 years). Their preoperative Glasgow Coma Scale scores ranged from 3 to 13 (mean, 6.9). The hematoma volumes ranged from 33.4 to 98.1 mL (mean, 74.2 mL), and the hematoma locations were the basal ganglia in 10 patients and the subcortex in 11 patients. Intraventricular extensions were observed in 11 patients. With regard to the complications after DC, postoperative hydrocephalus developed in ten patients, and meningitis was observed in three patients. Six patients had favorable outcomes and 15 had poor outcomes. The mortality rate was 10 %. A statistical analysis showed that the GCS score at admission was significantly higher in the favorable outcome group than that in the poor outcome group (P = 0.029). Our results suggest that DC with hematoma evacuation might be a useful surgical procedure for selected patients with large hemispheric hypertensive ICH 6).


Fung et al. compared consecutive patients (November 2010-January 2012) with supratentorial ICH treated with DC without hematoma evacuation and matched controls treated by best medical treatment. DC measured at least 150 mm and included opening of the dura. We analyzed clinical (age, sex, pathogenesis, Glasgow Coma Scale, National Institutes of Health Stroke Scale), radiological (signs of herniation, side and size of hematoma, midline shift, hematoma expansion, distance to surface), and surgical (time to and indication for surgery) characteristics. Outcome at 6 months was dichotomized into good (modified Rankin Scale 0-4) and poor (modified Rankin Scale 5-6).

Twelve patients (median age 48 years; interquartile range 35-58) with ICH were treated by DC. Median hematoma volume was 61.3 mL (interquartile range 37-83.5 mL) and median preoperative Glasgow Coma Scale was 8 (interquartile range 4.3-10). Four patients showed signs of herniation. Nine patients had good and 3 had poor outcomes. Three patients (25%) of the treatment group died versus 8 of 15 (53%) of the control group. There were 3 manageable complications related to DC.

DC is feasible in patients with ICH. Based on this small cohort, DC may reduce mortality. Larger prospective cohorts are warranted to assess safety and efficacy 7).


Records of 12 consecutive patients with hypertensive ICH treated with decompressive hemicraniectomy were reviewed. The data collected included Glasgow Coma Scale (GCS) score at admission and before surgery, ICH volume, ICH score, and a clinical grading scale for ICH that accurately risk-stratifies patients regarding 30-day mortality. Outcome was assessed as immediate mortality and modified Rankin Score (mRS) at the last follow-up.

Of the 12 patients with decompressive hemicraniectomy, 11 (92%) survived to discharge; of those 11, 6 (54.5%) had good functional outcome, defined as a mRS of 0 to 3 (mean follow-up: 17.13 months; range: 2-39 months). The mean age was 49.8 years (range: 19-76 years). Three of the 7 patients with pupillary abnormalities made a good recovery; of the 11 patients with intraventricular extensions (IVEs), 7 made a good recovery. The clinical finding (which was present in all 3 patients with mRS equal to 5 and which was not present in patients with mRS less than 5) was abnormal occulocephalic reflex. Of the 10 patients with an ICH score of 3, 9 (90%) survived to discharge, 4 (44%) had good functional outcome (mRS: 1-3). Hematoma volume was 60 cm3 or greater in eight patients, four (50%) of whom had good functional outcome (mRS: 0-3).

Decompressive hemicraniectomy with hematoma evacuation is life-saving and improves unfavorable outcomes in a select group of young patients with large right hemispherical ICH 8).

References

1)

Yao Z, Ma L, You C, He M. Decompressive Craniectomy for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis. World Neurosurg. 2018 Feb;110:121-128. doi: 10.1016/j.wneu.2017.10.167. Epub 2017 Nov 10. Review. PubMed PMID: 29129764.
2)

Marinkovic I, Strbian D, Pedrono E, Vekovischeva OY, Shekhar S, Durukan A, Korpi ER, Abo-Ramadan U, Tatlisumak T. Decompressive craniectomy for intracerebral hemorrhage. Neurosurgery. 2009 Oct;65(4):780-6, 1 p following 786; discussion 786. doi: 10.1227/01.NEU.0000351775.30702.A9. PubMed PMID: 19834384.
3)

Rasras S, Safari H, Zeinali M, Jahangiri M. Decompressive hemicraniectomy without clot evacuation in supratentorial deep-seated intracerebral hemorrhage. Clin Neurol Neurosurg. 2018 Aug 23;174:1-6. doi: 10.1016/j.clineuro.2018.08.017. [Epub ahead of print] PubMed PMID: 30172088.
4)

Lo YT, See AAQ, King NKK. Decompressive Craniectomy in Spontaneous Intracerebral Hemorrhage: A Case-Control Study. World Neurosurg. 2017 Jul;103:815-820.e2. doi: 10.1016/j.wneu.2017.04.025. Epub 2017 Apr 17. PubMed PMID: 28427977.
5)

Fung C, Murek M, Klinger-Gratz PP, Fiechter M, Z’Graggen WJ, Gautschi OP, El-Koussy M, Gralla J, Schaller K, Zbinden M, Arnold M, Fischer U, Mattle HP, Raabe A, Beck J. Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage. PLoS One. 2016 Feb 12;11(2):e0149169. doi: 10.1371/journal.pone.0149169. eCollection 2016. PubMed PMID: 26872068; PubMed Central PMCID: PMC4752325.
6)

Takeuchi S, Takasato Y, Masaoka H, Hayakawa T, Yatsushige H, Shigeta K, Nagatani K, Otani N, Nawashiro H, Shima K. Decompressive craniectomy with hematoma evacuation for large hemispheric hypertensive intracerebral hemorrhage. Acta Neurochir Suppl. 2013;118:277-9. doi: 10.1007/978-3-7091-1434-6_53. PubMed PMID: 23564148.
7)

Fung C, Murek M, Z’Graggen WJ, Krähenbühl AK, Gautschi OP, Schucht P, Gralla J, Schaller K, Arnold M, Fischer U, Mattle HP, Raabe A, Beck J. Decompressive hemicraniectomy in patients with supratentorial intracerebral hemorrhage. Stroke. 2012 Dec;43(12):3207-11. doi: 10.1161/STROKEAHA.112.666537. Epub 2012 Oct 30. PubMed PMID: 23111437.
8)

Murthy JM, Chowdary GV, Murthy TV, Bhasha PS, Naryanan TJ. Decompressive craniectomy with clot evacuation in large hemispheric hypertensive intracerebral hemorrhage. Neurocrit Care. 2005;2(3):258-62. PubMed PMID: 16159072.

UpToDate: Spontaneous posterior fossa subdural hematoma

Spontaneous posterior fossa subdural hematoma

Posterior fossa subdural hematomas may be spontaneous, with no previous trauma. These cases are usually secondary to bleeding from an underlying pathology such as arteriovenous malformation (AVM), aneurysm 1),tumor or coagulation disorder2) 3).

see also Spontaneous retroclival subdural hematoma.

Posterior fossa craniectomy may be preferable in terms of diagnosis and safe treatment 4).

Outcome

Prognosis seems to be related to the clinical condition of the patient at the moment of surgery, according to the GCS. Patients with mild symptomatology usually have a good outcome, whereas, in most cases, there is no improvement if a moderate or severe neurologic deficit has already been established 5) 6).

Case reports

Finger G, Martins OG, Basso LS, Ludwig do Nascimento T, Schiavo FL, Cezimbra Dos Santos S, Stefani MA. Acute spontaneous subdural hematoma in posterior fossa: case report with great outcome. World Neurosurg. 2018 Aug 1. pii: S1878-8750(18)31700-5. doi: 10.1016/j.wneu.2018.07.220. [Epub ahead of print] PubMed PMID: 30077031.


A 69-year-old woman was admitted with nausea, headache, and mild consciousness disturbance. Computed tomography and magnetic resonance imaging showed bilateral pCSH. To prevent further neurological deterioration, we performed surgery under general anesthesia by midline suboccipital craniectomy. Unexpected bleeding from a developed circuitous occipital sinus was stopped with hemoclips. After hematoma removal, she recovered and was transferred to a rehabilitation hospital. By the 19(th) postoperative day, she had developed no neurologic deficits.

This experience demonstrates the risk of blind surgical therapy in patients with pCSH. In such patients, posterior fossa craniectomy may be preferable in terms of diagnosis and safe treatment 7).


A 83-year-old woman was admitted with recent sudden headache and dizziness. Magnetic resonance imaging showed a thin collection of blood in the subdural space adjacent to the clivus, along the wall of the posterior fossa, and at the cervical spine level. A right posterior communicating artery aneurysm was diagnosed using computed tomography angiography and digital subtraction angiography. The aneurysm had two lobes, one of which was attached to the right dorsum sellae. The aneurysm was occluded by stent-assisted coil embolization. The patient was discharged 3 weeks after admission with absence of neurological deficit.

A ruptured aneurysm of the posterior communicating artery may cause an acute SDH 8).


A rare case of concomitant cranial and spinal subdural haematoma (SDH) in a 12-year-old boy with severe thrombocytopenia due to aplastic anaemia, and review the available literature. Magnetic resonance (MR) imaging at presentation revealed a cranial SDH confined to the posterior fossa, and spinal SDH extending from the C1 to S3 segments. The child was managed conservatively due to his poor general condition and lack of any neurological deficit. Repeat MR imaging done at six weeks showed complete resolution of the spinal SDH and partial resolution of the cranial SDH. Although rare, a spontaneous spinal SDH can occur simultaneously with a cranial SDH. Urgent surgical decompression is considered the treatment of choice for spinal SDH; however, a conservative approach may succeed in patients with poor general condition, and/or mild/no neurological deficit 9).


Berhouma M, Houissa S, Jemel H, Khaldi M. Spontaneous chronic subdural hematoma of the posterior fossa. J Neuroradiol. 2007 Jul;34(3):213-5. PubMed PMID: 17572494 10).


Usul et al., present a spontaneous posterior fossa subdural hematoma in a term neonate and discuss conservative management 11).


A case of spontaneous acute subdural haematoma in the posterior fossa following anticoagulation 12).


The association of the posterior fossa chronic subdural hematoma with spontaneous parenchymal hemorrhage without anticoagulation therapy was never related in the literature. Costa et al., describe a case of a 64 year-old woman who suffered a spontaneous cerebellar hemorrhage, treated conservatively, and presented 1 month later with a chronic subdural posterior fossa hematoma 13).


Miranda et al., present a case of a posterior fossa acute subdural hematoma occurring in an anticoagulated patient who was preoperatively misdiagnosed as an intracerebellar hemorrhage 14).


A 52-year-old woman treated for acute myeloproliferative disease developed progressive stupor. CT showed obstructive hydrocephalus resulting from unexplained mass effect on the fourth ventricle. MRI revealed bilateral extra-axial collections in the posterior cranial fossa, giving high signal on T1- and T2-weighted images, suggesting subacute subdural haematomas. Subdural haematomas can be suspected on CT when there is unexplained mass effect. MRI may be essential to confirm the diagnosis and plan appropriate treatment 15).


A 70 year old female presented with progressive dizziness, vertigo and gait ataxia. She was on anticoagulation therapy for heart disease. Neuro-imaging revealed bilateral infratentorial subdural masses. The subdural masses were suspects for chronic subdural haematomas by neuroradiological criteria. Because of the progressive symptomatology, the haematomas were emptied through burrhole trepanations. Chocolate-colored fluid, not containing clotted components, gushed out under great pressure. The source of bleeding could not be identified. The patient recovered well from surgery, but died 4 months later shortly after admission to another hospital from heart failure.

The chronic subdural haematomas in this patient may have been due to rupture of bridging veins caused by a very mild trauma not noticed by the patient and possibly aggravated by the anticoagulation therapy. Infratentorial chronic subdural haematoma should at least be a part of the differential diagnosis in elderly patients with cerebellar and vestibular symptomatology even without a history of trauma 16).


A case of spontaneous acute subdural hematoma complicated with idiopathic thrombocytopenic purpura was reported. He was hospitalized complaining of sudden onset of headache and nasal bleeding without neurological deficit. CT scan revealed subdural hematoma in the posterior fossa especially below the tentorium cerebelli. Further hematological examination proved very low platelet count (1,000/mm3) and antiplatelet antibody in confirmation of a diagnosis of idiopathic thrombocytopenic purpura. As his neurological status was good, he was treated medically. His symptoms and platelet count improved gradually with corticosteroid therapy. Reviewing the literature, acute subdural hematoma with idiopathic thrombocytopenic purpura was quite rare and only three cases reported 17).


Aicher KP, Heiss E, Gawlowski J. [Spontaneous subdural hematoma in the posterior cranial fossa]. Rofo. 1988 Dec;149(6):669-70. German. PubMed PMID: 2849170 18).


Kanter et al., report a patient in whom a spontaneous subdural hematoma developed in the posterior fossa during anticoagulation therapy for mitral valve disease. This rare complication of anticoagulation has been reported in only three other patients 19).


A case of spontaneous posterior fossa subdural hematoma secondary to anticoagulation therapy with definitive diagnosis made by vertebral angiography is reported. Vertebral angiographic findings are illustrated and demonstrate primarily mass effect from posterior compartment of posterior fossa and avascular area. Carotid angiography did not show hydrocephalus. A review of the literature was made and this appears to be the first reported case in which a posterior fossa subdural hematoma has been diagnosed by vertebral angiography 20).


A report of spontaneous posterior fossa subdural haematoma associated with anticoagulation therapy. The possibility of posterior fossa lesions related to spontaneous haemorrhage is suggested by the combination of severe headache and increasing disturbance of consciousness associated with signs of brain-stem decompensation. A thorough neurological evaluation including appropriate contrast studies will help rule out a supratentorial lesion. This is a neurological emergency which can be successfully treated by early detection and prompt surgical decompression. This is the second reported case of spontaneous subdural haematoma of the posterior fossa occurring during anticoagulant therapy 21).

References

1) , 8)

Kim MS, Jung JR, Yoon SW, Lee CH. Subdural hematoma of the posterior fossa due to posterior communicating artery aneurysm rupture. Surg Neurol Int. 2012;3:39. doi: 10.4103/2152-7806.94287. Epub 2012 Mar 24. PubMed PMID: 22530173; PubMed Central PMCID: PMC3327002.
2) , 16)

Stendel R, Schulte T, Pietilä TA, Suess O, Brock M. Spontaneous bilateral chronic subdural haematoma of the posterior fossa. Case report and review of the literature. Acta Neurochir (Wien). 2002 May;144(5):497-500. Review. PubMed PMID: 12111507.
3) , 10)

Berhouma M, Houissa S, Jemel H, Khaldi M. Spontaneous chronic subdural hematoma of the posterior fossa. J Neuroradiol. 2007 Jul;34(3):213-5. PubMed PMID: 17572494.
4) , 7)

Takemoto Y, Matsumoto J, Ohta K, Hasegawa S, Miura M, Kuratsu J. Bilateral posterior fossa chronic subdural hematoma treated with craniectomy: Case report and review of the literature. Surg Neurol Int. 2016 May 6;7(Suppl 10):S255-8. doi: 10.4103/2152-7806.181979. eCollection 2016. PubMed PMID: 27213111; PubMed Central PMCID: PMC4866054.
5) , 14)

Miranda P, Alday R, Lagares A, Pérez A, Lobato RD. Posterior fossa subdural hematoma mimicking intracerebellar hemorrhage. Neurocirugia (Astur). 2003 Dec;14(6):526-8. PubMed PMID: 14710308.
6) , 15)

Pollo C, Meuli R, Porchet F. Spontaneous bilateral subdural haematomas in the posterior cranial fossa revealed by MRI. Neuroradiology. 2003 Aug;45(8):550-2. Epub 2003 May 22. PubMed PMID: 12761603.
9)

Jain V, Singh J, Sharma R. Spontaneous concomitant cranial and spinal subdural haematomas with spontaneous resolution. Singapore Med J. 2008 Feb;49(2):e53-8. Review. PubMed PMID: 18301828.
11)

Usul H, Karaarslan G, Cakir E, Kuzeyl K, Mungan L, Baykal S. Conservative management of spontaneous posterior fossa subdural hematoma in a neonate. J Clin Neurosci. 2005 Feb;12(2):196-8. PubMed PMID: 15749432.
12)

Pal D, Gnanalingham K, Peterson D. A case of spontaneous acute subdural haematoma in the posterior fossa following anticoagulation. Br J Neurosurg. 2004 Feb;18(1):68-9. PubMed PMID: 15040720.
13)

Costa LB Jr, de Andrade A, Valadão GF. Chronic subdural hematoma of the posterior fossa associated with cerebellar hemorrhage: report of rare disease with MRI findings. Arq Neuropsiquiatr. 2004 Mar;62(1):170-2. Epub 2004 Apr 28. PubMed PMID: 15122456.
17)

Saito K, Sakurai Y, Uenohara H, Seki K, Imaizumi S, Katakura R, Niizuma H. [A case of acute subdural hematoma in the posterior fossa with idiopathic thrombocytopenic purpura]. No To Shinkei. 1992 Apr;44(4):377-81. Review. Japanese. PubMed PMID: 1633035.
18)

Aicher KP, Heiss E, Gawlowski J. [Spontaneous subdural hematoma in the posterior cranial fossa]. Rofo. 1988 Dec;149(6):669-70. German. PubMed PMID: 2849170.
19)

Kanter R, Kanter M, Kirsch W, Rosenberg G. Spontaneous posterior fossa subdural hematoma as a complication of anticoagulation. Neurosurgery. 1984 Aug;15(2):241-2. PubMed PMID: 6483141.
20)

McClelland RR, Ramirez-Lassepas M. Posterior fossa subdural hematoma demonstrated by vertebral angiography. Neuroradiology. 1976;10(1):181-5. PubMed PMID: 1256644.
21)

Capistrant T, Goldberg R, Shibasaki H, Castle D. Posterior fossa subdural haematoma associated with anticoagulant therapy. J Neurol Neurosurg Psychiatry. 1971 Feb;34(1):82-5. PubMed PMID: 5313648; PubMed Central PMCID: PMC493691.

UpToDate: Internal carotid artery segments

Internal carotid artery segments

The course of the internal carotid artery (ICA) and its segment classifications were reviewed by means of a new and freely available interactive 3D model of the artery and the skull base, based on human neuroimages, that can be freely downloaded at the Public Repository of the University of Barcelona ( http://diposit.ub.edu/dspace/handle/2445/112442 ) and runs under Adobe Acrobat Reader in Mac and Windows computers and Windows 10 tablets. The 3D-PDF allows zoom, rotation, selective visualization of structures, and a predefined sequence view. Illustrative images of the different classifications were obtained 1).

In 1938 Fischer, described five internal carotid artery segments in the opposite direction to the blood flow 2).

These segments were based on the angiographic course of the intracranial ICA rather than its arterial branches or anatomic compartments. Subsequent attempts to apply modern nomenclature to these numerical segments failed to recognize Fischer’s original intent of describing patterns of arterial displacement by tumors and, therefore, resulted in a nomenclature that was anatomically inaccurate. Fischer’s system was further limited, because segments were numbered opposite the direction of blood flow and the extracranial ICA was excluded 3).


Gibo et al. in 1981 studied the microsurgical anatomy of the supraclinoid portion of the internal carotid artery (ICA) in 50 adult cadaver cerebral hemispheres using X 3 to X 40 magnification. The ICA was divided into four parts: the C1 or cervical portion; the C2 or petrous portion; the C3 or cavernous portion; and the C4 or supraclinoid portion.

The C4 portion was divided into three segments based on the origin of its major branches: the ophthalmic segment extended from the origin of the ophthalmic artery to the origin of the posterior communicating artery (PCoA); the communicating segment extended from the origin of the PCoA to the origin of the anterior choroidal artery (AChA); and the choroidal segment extended from the origin of the AChA to the bifurcation of the carotid artery. Each segment gave off a series of perforating branches with a relatively constant site of termination. The perforating branches arising from the ophthalmic segment passed to the optic nerve and chiasminfundibulum, and the floor of the third ventricle. The perforating branches arising from the communicating segment passed to the optic tract and the floor of the third ventricle. The perforating branches arises from the choroidal segment passed upward and entered the brain through the anterior perforated substance. The anatomy of the ophthalmic, posterior communicating, anterior choroidal, and superior hypophyseal branches of the C4 portion was also examined. Gibo-Rothon (J Neurosurg 55:560-574, 1981) follow the blood flow, incorporated the cervical and petrous portions, and divided the subarachnoid course-supraclinoid-in ophthalmic, communicating, and choroidal segments, enhancing transcranial microscopic approaches 4).


see Bouthillier classification.

Bouthillier et al. described in 1996 a seven segment internal carotid artery (ICA) classification system. It remains the most widely used system for describing ICA segments.


The Kassam’s group (2014), with an endoscopic endonasal perspective, introduces the “paraclival segment,” including the “lacerum segment” and part of the intracavernous ICA, and details surgical landmarks to minimize the risk of injury 5).

see also Carotid Siphon

AC: anterior clinoid process; ICA: internal carotid artery; LT: lamina terminalis; ON: optic nerve; OlN; olfactory nerve; SW: sphenoid wing; TS: tuberculum sellae; A1: A1 segment of the Anterior Cerebral Artery; A2: A2 segment of the Anterior Cerebral Artery; M1: M1 segment of the Middle Cerebral Artery

Endoscopic classification

Based on anatomic correlations, the ICA may be described as 6 distinct segments:

(1) parapharyngeal (common carotid artery bifurcation to carotid canal)

(2) petrous (carotid canal to posterolateral aspect of foramen lacerum)

(3) paraclival (posterolateral foramen lacerum to the superomedial aspect of the petrous apex)

(4) parasellar (superomedial petrous apex to the proximal dural ring)

(5) paraclinoid (from the proximal to the distal dural rings)

(6) intradural (distal ring to ICA bifurcation).

Corresponding surgical landmarks included the Eustachian tube, the fossa of Rosenmüller, and levator veli palatini for the parapharyngeal segment; the vidian canal and V3 for the petrous segment; the fibrocartilage of foramen lacerumforamen rotundummaxillary strut, lingular process of the sphenoid bone, and paraclival protuberance for the paraclival segment; the sellar floor and petrous apex for the parasellar segment; and the medial and lateral opticocarotid and lateral tubercular recesses, as well as the distal osseous arch of the carotid sulcus for the paraclinoid segment 6).

see Intracavernous internal carotid artery.

References

1)

Melé MV, Puigdellívol-Sánchez A, Mavar-Haramija M, Juanes-Méndez JA, Román LS, De Notaris M, Catapano G, Prats-Galino A. Review of the main surgical and angiographic-oriented classifications of the course of the internal carotid artery through a novel interactive 3D model. Neurosurg Rev. 2018 Jul 26. doi: 10.1007/s10143-018-1012-7. [Epub ahead of print] Review. PubMed PMID: 30051302.
2)

Fischer E. Die Lageabweichungen der vorderen hirnarterie im gefässbild. Zentralbl Neurochir. 1938;3:300–313.
3)

Bouthillier A, van Loveren HR, Keller JT. Segments of the internal carotid artery: a new classification. Neurosurgery. 1996 Mar;38(3):425-32; discussion 432-3. PubMed PMID: 8837792.
4)

Gibo H, Lenkey C, Rhoton AL Jr. Microsurgical anatomy of the supraclinoid portion of the internal carotid artery. J Neurosurg. 1981 Oct;55(4):560-74. PubMed PMID: 7277004.
5) , 6)

Labib MA, Prevedello DM, Carrau R, Kerr EE, Naudy C, Abou Al-Shaar H, Corsten M, Kassam A. A road map to the internal carotid artery in expanded endoscopic endonasal approaches to the ventral cranial base. Neurosurgery. 2014 Sep;10 Suppl 3:448-71. doi: 10.1227/NEU.0000000000000362. PubMed PMID: 24717685.

UptoDate: Indocyanine green videoangiography for intracranial aneurysm

Indocyanine green videoangiography for intracranial aneurysm

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

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

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

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

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

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

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

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

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

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

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

References

1)

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

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

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

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

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

UpToDate: Agitation

Agitation

Hyperactive delirium (agitation) is an emotional state of excitement or restlessness.

Hyperactive delirium (agitation) is a common complication in patients on intensive care units.

Psychomotor agitation, an extreme form of the above, which can be part of a mental illness or a side effect of anti-psychotic medication.

Assesment

Sedation Agitation Scale.


Postoperative agitation frequently occurs after general anesthesia and may be associated with serious consequences. However, studies in neurosurgical patients have been inadequate.

Huang et al., from the Beijing Tiantan Hospital and the Mongolia People’s Hospital, China. aimed to investigate the incidence and risk factors for early postoperative agitation in patients after craniotomy, specifically focusing on the association between postoperative pneumocephalus and agitation. Adult intensive care unit admitted patients after elective craniotomy under general anesthesia were consecutively enrolled. Patients were assessed using the Sedation Agitation Scale during the first 24 hours after operation. The patients were divided into two groups based on their maximal Sedation-Agitation Scale: the agitation (Sedation-Agitation Scale ≥ 5) and non-agitation groups (Sedation-Agitation Scale ≤ 4). Preoperative baseline data, intraoperative and intensive care unit admission data were recorded and analyzed. Each patient’s computed tomography scan obtained within six hours after operation was retrospectively reviewed. Modified Rankin Scale and hospital length of stay after the surgery were also collected. Of the 400 enrolled patients, agitation occurred in 13.0% (95% confidential interval: 9.7-16.3%). Body mass index, total intravenous anesthesia, intraoperative fluid intake, intraoperative bleeding and transfusionconsciousness after operation, endotracheal intubation kept at intensive care unit admission and mechanical ventilation, hyperglycemia without a history of diabetes, self-reported pain and postoperative bi-frontal pneumocephalus were used to build a multivariable model. Bi-frontal pneumocephalus and delayed extubation after the operation were identified as independent risk factors for postoperative agitation. After adjustment for confounding, postoperative agitation was independently associated with worse neurologic outcome (odd ratio: 5.4, 95% confidential interval: 1.1-28.9, P = 0.048).

The results showed that early postoperative agitation was prevalent among post-craniotomy patients and was associated with adverse outcomes. Improvements in clinical strategies relevant to bi-frontal pneumocephalus should be considered 1).


Sauvigny et al., from the University Medical Centre Hamburg-Eppendorf Germany, performed a retrospective analysis in three hundred thirty-eight patients with aneurysmal subarachnoid hemorrhage resulting in 212 patients which reached at least once a Richmond Sedation Agitation Scale(RASS) of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up.

They provided four independent risk factors for the development of agitation in SAH patients. The study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients 2).

References

1)

Huang HW, Yan LM, Yang YL, He X, Sun XM, Wang YM, Zhang GB, Zhou JX. Bi-frontal pneumocephalus is an independent risk factor for early postoperative agitation in adult patients admitted to intensive care unit after elective craniotomy for brain tumor: A prospective cohort study. PLoS One. 2018 Jul 19;13(7):e0201064. doi: 10.1371/journal.pone.0201064. eCollection 2018. PubMed PMID: 30024979.
2)

Sauvigny T, Mohme M, Grensemann J, Dührsen L, Regelsberger J, Kluge S, Schmidt NO, Westphal M, Czorlich P. Rate and risk factors for a hyperactivity delirium in patients with aneurysmal subarachnoid haemorrhage. Neurosurg Rev. 2018 Jun 9. doi: 10.1007/s10143-018-0990-9. [Epub ahead of print] PubMed PMID: 29948495.

UptoDate: Medulla Oblongata Cavernous Malformation

Medulla Oblongata Cavernous Malformation

see also Brainstem cavernous malformation.

53 patients underwent surgical treatment for Medulla Oblongata Cavernous Malformations between 2011 and 2017 in the Beijing Tiantan Hospital with a male-to-female ratio of 1.4 and a mean age of 32.6 years. Eighteen patients (34.0%) had respiratory failure, and two patients (3.8%) had cardiac instabilities, preoperatively. The mean mRS score was 2.7 upon admission. Gross total resection was achieved in 52 patients (98.1%). Postoperatively, twenty-three patients (43.4%) had respiratory dysfunction, and sixteen patients (30.2%) had dysphagia or coughing. The mean follow-up duration was 35.7 months. At the last follow-up evaluation, the mean mRS score was 1.7, and 42 patients (84%) had favorable outcomes, with mRS scores ≤ 2. The conditions of the patients improved in 34 cases (68%), remained unchanged in 10 cases (20%), and worsened in 6 cases (12%) relative to the preoperative baseline. The independent adverse factors for long-term outcome were age ≥ 50 years old and increased time of reservation of tracheal intubationafter surgery.

Surgical treatment of CMs involving the medulla oblongata was very challenging, notably, perioperative respiratory dysfunction, with which patients tend to have unfavorable long-term outcomes, especially for elderly patients 1).


A 28-year-old man who was presented with intractable hiccup for 15 days. It developed suddenly, then aggravated progressively and did not respond to any types of medication. On magnetic resonance images, a well-demarcated and non-enhancing mass with hemorrhagic changes was noted in the left medulla oblongata. Intraoperative findings showed that the lesion was fully embedded within the brain stem and pathology confirmed the diagnosis of cavernous hemangioma. The hiccup resolved completely after the operation. Based on the presumption that the medullary cavernoma may trigger intractable hiccup by displacing or compression the hiccup arc of the dorsolateral medulla, surgical excision can eliminate the symptoms, even in the case totally buried in brainstem 2).


A 61-year-old woman presented with vertigo and swallowing disturbance. T1-weighted magnetic resonance image (MRI) showed a low intensity mass in the dorsolateral portion of the medulla oblongata, and T2-weighted imaging revealed a hemosiderin rim surrounding the lesion. Angiography showed no abnormalities. Surgery using far lateral approach achieved complete removal of the mass and hematoma. Histological examination of the surgical specimen disclosed cavernous angioma. This case suggests that direct surgery can be recommended for cavernous angioma located in the dorsal or lateral medulla oblongata to remove the hematoma and angioma if bleeding clearly provokes neurological symptoms 3).

1)

Xie MG, Xiao XR, Li D, Guo FZ, Zhang JT, Wu Z, Zhang LW. Surgical Treatment of Cavernous Malformations Involving the Medulla Oblongata: 53 Cases. World Neurosurg. 2018 Jul 4. pii: S1878-8750(18)31429-3. doi: 10.1016/j.wneu.2018.06.213. [Epub ahead of print] PubMed PMID: 29981463.
2)

Lee KH, Moon KS, Jung MY, Jung S. Intractable hiccup as the presenting symptom of cavernous hemangioma in the medulla oblongata: a case report and literature review. J Korean Neurosurg Soc. 2014 Jun;55(6):379-82. doi: 10.3340/jkns.2014.55.6.379. Epub 2014 Jun 30. PubMed PMID: 25237438; PubMed Central PMCID: PMC4166338.
3)

Abe M, Ogawa A, Yoshida Y, Hidaka T, Suzuki M, Takahashi S. Surgical removal of cavernous angioma in the medulla oblongata. A case report. Neurosurg Rev. 1997;20(2):128-31. Review. PubMed PMID: 9226673.

UpToDate: Astragaloside IV

Astragaloside IV

Astragaloside IV (AS IV) is a saponin purified from a traditional Chinese herbal medicine component Astragalus membraneaceus (Fisch.) Bunge 1)2).

Astrageloside IV has broad application prospects, especially in cardiovascular diseases, digestive diseases, cancer and other modern high incidence, high-risk diseases, and could be developed as a medicine 3).

Delayed cerebral ischemia is an important cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH).

A rat model of SAH was established by puncturing one side of the internal carotid artery. Then, rats received daily intraperitoneal injections of Astragaloside IV (AS-IV) (20 mg/kg; SAH-AS-IV group), 0.1% DMSO (SAH-DMSO group) or saline (SAH group) for 5 days; an additional control group consisted of rats receiving sham surgery and saline injections. Morphological characteristics of the basilar artery (BA) were measured from histological sections stained with hematoxylin-eosin, and used as indicators of cerebral vasospasm. Immunohistochemistry was used to detect toll-like receptor-4 (TLR4) and nuclear factor kappa B (NF-κBp65 protein levels in the BA. Enzyme-linked immunosorbent assay was used to measure the plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6).

Compared with controls, the SAH-DMSO and SAH groups showed increased wall thickness and reduced luminal cross-sectional area (indicative of vasospasm), and increased TLR4 expression and enhanced NF-κB activation in the BA, as well as elevated plasma levels of TNF-α and IL-6. Administration of AS-IV was associated with significant attenuation of all the above changes induced by SAH (P<0.05).

AS-IV may attenuate delayed cerebral vasospasm after SAH through inhibition of TLR4/NF-κB-mediated inflammatory signaling pathways 4).


Li et al., found that astragaloside IV (10 and 20mg/kg) significantly attenuated the cerebral water content (P<0.05) and improved neurological outcomes (P<0.05) in comparison with vehicle group. Moreover, we investigate the effect of astragaloside IV on the (blood-brain barrier) BBB since cerebral edema was closely related to the permeability of the BBB. We found that the permeability of BBB was improved significantly in astragaloside IV groups compared with vehicle group via Evans blue leakage (P<0.05). This was further confirmed under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in vehicle group. In drug groups, lanthanum stain was mainly restricted within the cerebral capillary, indicating the potential BBB-protective effect of astragaloside IV. Furthermore, we found that expressions of Matrix metalloproteinase-9 (MMP-9) and aquaporin 4 (AQP4) were increased in vehicle group, which were related to cerebral vasogenic edema or cytotoxic edema. The up-regulations of MMP-9 and AQP4 were inhibited significantly by astragaloside IV administration. We propose that the anti-edema potential of astragaloside IV was correlated with its regulation of MMP-9 and AQP4 5).


Li et al., studied the potential of astragaloside IV, one of the major and active components of the astragalus membranaceous, to protect rat against cerebral inflammation injury elicited by focal cerebral ischemia and reperfusion and related protective mechanisms. The rat model was induced by intraluminal occlusion of the right middle cerebral artery with reperfusion. Animals received astragaloside IV (10 or 20 mg/kg) injections when reperfusion was began to. Neurobehavioral evaluation and infarct assessment were studied. Myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). The rates of CD11b/CD18-positive neutrophils were analyzed via flow cytometry. Intercellular adhesion molecule-1 (ICAM-1) and nuclear factor κB (NF-κB) were measured by immunohistochemistry and Western blot. Astragaloside IV improved neurological outcome and reduced infarct volume at 24 h after reperfusion. The protective effect was achieved by preventing neutrophils accumulation in the brain parenchyma demonstrated by significantly reducing the concentration of MPO in brain tissue. Astragaloside IV exerts the protection through remarkably decreasing the percentage of CD11b/CD18-positive neutrophils and down-regulating the expression of intercellular adhesion molecule-1 (ICAM-1), which is partly achieved by strongly attenuating the production of TNF-α and IL-1β and inhibiting level of nuclear factor-κB (NF-κB). We propose an anti-inflammatory mechanism evoked by astragaloside IV by suppression of neutrophils adhesion-related molecules, which exerts neuroprotection against I/R injury 6).


Zhang et al., investigated whether AS-IV protect against 1-methyl-4-phenylpyridnium ion (MPP(+))-induced dopaminergic neurotoxicity in SH-SY5Y cells and determined the mechanism of AS-IV neuroprotection. We found that pretreatment with AS-IV significantly reversed the loss of cell viability, nuclear condensation, the generation of intracellular reactive oxygen species (ROS), and the increase in Bax/Bcl-2 ratio and the activity of caspase-3 induced by MPP(+). Our study suggests that the neuroprotective effect of AS-IV is related to mechanisms including ROS production and the inhibition of Bax-mediated pathway. The present study supports the notion that AS-IV may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as PD 7).


Qu et al., found that astragaloside IV (10, 20 mg/kg) significantly attenuated the permeability of blood-brain barrier in comparison with vehicle group after ischemia/reperfusion assessed via Evans blue leakage (P<0.05). This was further confirmed by examination of blood-brain barrier permeability under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in vehicle group. In drug groups, lanthanum stain was mainly restricted within the cerebral capillary, indicating the potential protective effect of astragaloside IV on the integrity of blood-brain barrier in ischemia/reperfusion rats. Furthermore, we found that expression of occludin and zonae occludens-1 (ZO-1), the tight junction proteins, was decreased in endothelial cells in vehicle group, which, however, could be reversed by astragaloside IV administration. We propose that regulation of tight junctional proteins in the endothelial cells may be one mechanism astragaloside IV-mediated in attribution to blood-brain barrier protection in the ischemia/reperfusion rats 8).


The aim of this study was to evaluate peripheral nerve regeneration across a 15-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve guide filled with different concentrations of astragaloside (0, 50, 100, and 200 microM). Collagen was also filled in the chambers to prevent the astragaloside from leakage. At the end of 8 weeks, animals from the group treated with astragaloside, especially at the concentration of 50 microM, had a higher rate of successful regeneration across the wide gap, a significantly larger number of myelinated axons, and a greater evoked action potential than the control group. However, the high-dose astragaloside (200 microM) completely reversed this positive effect of growth-promoting capability and inhibited nerve regeneration. Thus, astragaloside plays a dual role in anastomosis, being salutary in aiding the growth of axons in peripheral nerve but also detrimental, terminating the nerve regenerative processes if improperly applied 9).

1)

Li M, Wang W, Xue J, Gu Y, Lin S. Meta-analysis of the clinical value of Astragalus membranaceus in diabetic nephropathy. J Ethnopharmacol. 2011;133:412–419. doi: 10.1016/j.jep.2010.10.012.
2)

Matkovic Z, Zivkovic V, Korica M, Plavec D, Pecanic S, Tudoric N. Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis. Phytother Res. 2010;24:175–181.
3)

Ren S, Zhang H, Mu Y, Sun M, Liu P. Pharmacological effects of Astragaloside IV: a literature review. J Tradit Chin Med. 2013 Jun;33(3):413-6. Review. PubMed PMID: 24024343.
4)

Ma Y, Yin Y, Zhang Y, Yu Y, Yu X. Protective effects of Astragaloside IV on delayed cerebral vasospasm in an experimental rat model of subarachnoid hemorrhage. World Neurosurg. 2018 Jul 4. pii: S1878-8750(18)31428-1. doi: 10.1016/j.wneu.2018.06.212. [Epub ahead of print] PubMed PMID: 29981464.
5)

Li M, Ma RN, Li LH, Qu YZ, Gao GD. Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4. Eur J Pharmacol. 2013 Sep 5;715(1-3):189-95. doi: 10.1016/j.ejphar.2013.05.022. Epub 2013 Jun 5. PubMed PMID: 23747593.
6)

Li M, Qu YZ, Zhao ZW, Wu SX, Liu YY, Wei XY, Gao L, Gao GD. Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochem Int. 2012 Apr;60(5):458-65. doi: 10.1016/j.neuint.2012.01.026. Epub 2012 Feb 8. PubMed PMID: 22342823.
7)

Zhang ZG, Wu L, Wang JL, Yang JD, Zhang J, Zhang J, Li LH, Xia Y, Yao LB, Qin HZ, Gao GD. Astragaloside IV prevents MPP⁺-induced SH-SY5Y cell death via the inhibition of Bax-mediated pathways and ROS production. Mol Cell Biochem. 2012 May;364(1-2):209-16. doi: 10.1007/s11010-011-1219-1. Epub 2012 Jan 26. PubMed PMID: 22278385.
8)

Qu YZ, Li M, Zhao YL, Zhao ZW, Wei XY, Liu JP, Gao L, Gao GD. Astragaloside IV attenuates cerebral ischemia-reperfusion-induced increase in permeability of the blood-brain barrier in rats. Eur J Pharmacol. 2009 Mar 15;606(1-3):137-41. doi: 10.1016/j.ejphar.2009.01.022. Epub 2009 Jan 25. PubMed PMID: 19374856.
9)

Cheng CY, Yao CH, Liu BS, Liu CJ, Chen GW, Chen YS. The role of astragaloside in regeneration of the peripheral nerve system. J Biomed Mater Res A. 2006 Mar 1;76(3):463-9. PubMed PMID: 16315188.

UpToDate: Unruptured intracranial aneurysm rupture risk

Unruptured intracranial aneurysm rupture risk

There are substantial differences in patient and aneurysm characteristics between ruptured intracranial aneurysm and unruptured intracranial aneurysms. These findings support the hypothesis that different pathological mechanisms are involved in the formation of ruptured aneurysms and incidentally detected unruptured aneurysms. The potential protective effect of aspirin might justify randomized prevention trials in patients with unruptured aneurysms 1).

The exact prevalence of unruptured intracranial aneurysms (UIAs) is unknown, but at least one in 20 to 30 adults is likely to carry an asymptomatic UIA. Approximately one quarter of these UIAs rupture in a lifetime. Complex methodological challenges in conducting studies of epidemiology and risk factors for UIAs and SAH might have led to conclusions being drawn on the basis of epidemiological data of variable quality. Korja et al. believe that, as a result, misconceptions about UIAs and SAH may have arisen. They discuss three possible misconceptions about the epidemiology of UIAs and SAH, and suggest how the quality of future research could be improved 2).


Aneurysm location and other morphologic variables could play a role in predicting overall risk of rupture. Morphological parameters can be divided into 3 main groups, those that are intrinsic to the aneurysm, those that are extrinsic to the aneurysm, and those that involve both the aneurysm and surrounding vasculature (transitional).

By studying the morphology of aneurysms and their surrounding vasculature, Ho et al. identified several parameters associated with ruptured aneurysms that include intrinsic, transitional, and extrinsic factors of cerebral aneurysms and their surrounding vasculature 3).

see PHASES score

Despite the fact that ruptured intracranial aneurysm (RIAs) can be prevented by microsurgical clipping or endovascular coiling, there are no reliable means of effectively predicting IA patients at risk for rupture.

In patients of working age alcohol consumption and cigarette smoking are modifiable risk factors for untimely death through several causes and should be taken into account when treatment is considered 4).

Size

Unruptured saccular aneurysms less than 10 mm in diameter have a very low probability of subsequent rupture. The mean diameter of the aneurysms that subsequently ruptured was 21.3 mm, compared with a diameter of 7.5 mm for aneurysms defined after rupture at the same institution. Part of the explanation for this discrepancy may be that the size of the filling compartment of the aneurysm decreases after rupture. There is also evidence from a study that intracranial saccular aneurysms develop with increasing age of the patient and stabilize over a relatively short period, if they do not initially rupture, and that the likelihood of subsequent rupture decreases considerably if the initial stabilized size is less than 10 mm in diameter. Consequently, the critical size for aneurysm rupture is likely to be smaller if rupture occurs at the time of or soon after aneurysm formation. There seems to be a substantial difference in potential for growth and rupture between previously ruptured and unruptured aneurysms 5).

The annual rupture rate associated with small unruptured aneurysms is quite low. Careful attention should be paid to the treatment indications for single-type unruptured aneurysms <5 mm. If the patient is <50 years of age, has hypertension, and multiple aneurysms with diameters of >or=4 mm, treatment should be considered to prevent future aneurysmal rupture 6).

Cigarette smoking, patient age inversely, and the size and location of the unruptured intracranial aneurysm seem to be risk factors for aneurysm rupture. The risk of bleeding decreases with a very long-term follow-up 7).

The association of morphological characteristics with ruptured aneurysms has not been established in a systematic and location specific manner for the most common aneurysm locations.

Geometric or hemodynamic considerations

Geometric or hemodynamic considerations favor identification of rupture status; however, retrospective identification of the rupture site remains a challenge for both engineers and clinicians. A more precise understanding of the hemodynamic factors involved in aneurysm wall pathology is likely required for computational fluid dynamics to add value to current clinical decision-making regarding rupture risk 8).

Fragility of the aneurysmal wall

The fragility of the aneurysmal wall is an important predictive factor of rupture. Presently, however, it is difficult to determine when an operation for an unruptured tiny aneurysm is indicated; new neuroimaging techniques that detect the fragility of the aneurysmal wall are needed 9).


Fifty unruptured middle cerebral artery aneurysms were analyzed. Spatial and temporal maximum pressure (Pmax) areas were determined with a fluid-flow formula under pulsatile blood flow conditions. Intraoperatively, thin walled regions (TWRs) of aneurysm domes were identified as reddish areas relative to the healthy normal middle cerebral arteries; 5 neurosurgeons evaluated and divided these regions according to Pmax area and TWR correspondence. Pressure difference (PD) was defined as the degree of pressure elevation on the aneurysmal wall at Pmax and was calculated by subtracting the average pressure from the Pmax and dividing by the dynamic pressure at the aneurysm inlet side for normalization.

In 41 of the 50 cases (82.0%), the Pmax areas and TWRs corresponded. PD values were significantly higher in the correspondence group than in the noncorrespondence group (P = .008). A receiver-operating characteristic curve demonstrated that PD accurately predicted TWRs at Pmax areas (area under the curve, 0.764; 95% confidence interval, 0.574-0.955; cutoff value, 0.607; sensitivity, 66.7%; specificity, 82.9%).

A high PD may be a key parameter for predicting TWRs in unruptured cerebral aneurysms 10).

Suzuki et al., present in this issue the findings of their research on intracranial aneurysms and report the work on pressure elevations at the thin walled regions of an aneurysm dome using computational fluid dynamics (CFD) modeling in 51 unruptured middle cerebral artery aneurysms. The authors attempt to show that areas of maximum pressure may be important markers of thin-wall regions in unruptured cerebral aneurysms and theorize that by calculating the pressure difference value for each aneurysm type using computational fluid dynamics, it is possible to estimate the accuracies of predictions regarding thin-wall regions.It would seem that this is a good study and a worthwhile contribution to the literature. At the same time, it appears that not much has changed since Kallmes 11) wrote his poignant and perhaps provoking but timely editorial 4 years ago, and there continue to be publications that fail basic tests or internal consistency and validity.CFD modeling for intracranial aneurysms has emerged from an arcane interest of a few to a field producing a significant number of articles. A simple search in PubMed yields <2 results for the years 1990 to 1999 and >19 for the years 2015 to 2016 alone. This of course reflects the greater affordability and easier access to high-performance computing platforms, overall advances in computing power, and easier-to-use software packages complete with graphical user interfaces. A number of articles by very experienced researchers have questioned in the past the validity and value of CFD modeling 12) 13) 14) 15) 16) 17).

CFD analysis in particular is a field that is prone to data dredging and exploratory analysis. It should be considered paramount to raise the quality of the research done by requiring authors to clearly state the hypothesis tested in their work. It remains a basic, albeit often overlooked and perhaps at times consciously evaded, requirement for publication of research findings that the methods described allow a knowledgeable expert in the field to reproduce the findings. In line with the publishing of research in such a manner that it, in theory, could be reproducible and verifiable and with the almost limitless space offered by online supplementary data appendixes, we should call for, perhaps in an online appendix, a framework for defining physical quantities and boundary conditions and a demonstration that the modeling setup is able to reproduce parameters of basic known CFD experiments such as flow development in a curved tube or a stenotic tube. Demonstration of grid and mesh density independently of results should require authors to provide clearly stated definitions for these parameters and the details of their approximations in computational and experimental studies. This is especially important for research groups publishing their first results in this field, although perhaps less so for groups that can reference a body of previous works in which such testing of their setup was done in the past.CFD is exquisitely sensitive to assumptions made and boundary conditions entering the simulation, and results must be presented and analyzed with these assumptions in mind. Internal controls are difficult to come by, but it has been a best practice to explicitly describe the flow and wall parameter conditions in a assumed normal vessel segment. In other words, unless the simulation predicts a rather normal flow environment and wall shear conditions in the parent vessel of a side wall aneurysm proximal and distal to the aneurysmal segment, why abnormal values in the aneurysmal segment predicted by the simulation should be taken at face value deserves some explanation.

It is worth repeating the questions raised by Robertson and Watton 18) when conducting CFD research on intracranial aneurysms, asking to make judicious assumptions about boundary conditions, and an effort should be made to conduct an error or sensitivity analysis for assumptions that may influence the hemodynamics in the parent vessel tree and the aneurysm sac, especially when we have limited information about such assumptions. Idealizations are important and necessary tools for developing models and assumptions, but conclusions based on one specific anatomy may not hold up for other geometries. Using patient-based geometries but assuming the same inflow boundary condition for all cases would lead to unrealistic results, even when the model would be a simple straight vessel, disregarding the complication of an aneurysm attached to such a vessel. We know that shear conditions in a normal vessel are somewhat tightly regulated to ensure a healthy hemodynamic milieu for the endothelial cells.

The present publication not only adds another metric to the extensive table compiled by Xiang et al 19) but is more significant for the seemingly arbitrary construction of a dimensionless parameter called the pressure difference, which has the physical properties of a friction coefficient.

Perhaps on a more optimistic note, this continues to be a field with great potential, and more often than not, we see studies with innovative design and interesting approaches 20).

The value in simulation lies in linking physiological measurements to processes that cannot readily be measured but need to be quantified to explain the underlying mechanisms and processes and, in enhancing our understanding of these processes, to ultimately help our patients 21).


Posterior communicating artery aneurysm

Morphological parameters associated with aneurysm rupture in that location were evaluated to generate 3-D models of the aneurysms and surrounding vasculature. Univariate and multivariate analyses were performed to evaluate morphological parameters including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation, aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From 2005-2012, 148 PCoA aneurysms were treated in a single institution. Preoperative CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed. Multivariate logistic regression revealed that smaller volume (p = 0.011), larger aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance (p = 0.005) were the most strongly associated with aneurysm rupture after adjusting for all other clinical and morphological variables. Multivariate subgroup analysis for patients with visualized PCoA demonstrated that larger neck diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011) were significantly associated with rupture. Intracerebral hemorrhage was associated with smaller volume, larger maximum height, and smaller aneurysm angle, in addition to lateral projection, male sex, and lack of hypertension. Ho et al., found that shorter ICA bifurcation to aneurysm distance is significantly associated with PCoA aneurysm rupture. This is a new physically intuitive parameter that can be measured easily and therefore be readily applied in clinical practice to aid in the evaluation of patients with PCoA aneurysms22).

Case series

Murayama et al., 23) conservatively followed up a cohort of 1960 aneurysms for up to 10 years and performed a risk analysis of rupture. From January 2003 to December 2012, the authors enrolled 1556 patients with 1960 aneurysms of 2665 patients with 3434 aneurysms screened. Patients were eligible for the study if they had an aneurysm at least 2 mm in its largest dimension. Exclusion criteria included fusiform, traumatic, or mycotic aneurysms; treatment before enrollment in the study; carotid cavernous aneurysms; and infundibular dilations. The authors recommended observation for aneurysms <5 mm and treatment for aneurysms >10 mm. For aneurysms between 5 and 10 mm, risks of treatment vs observation were discussed with the patients. Patients were followed up until time of subarachnoid hemorrhage (SAH), death resulting from any cause, or last possible follow-up contact. Patients were divided into 2 groups. Group 1 was composed of patients with no history of SAH, and group 2 was composed of patients with a history of SAH. Patients who presented with signs and symptoms of mass effect were treated urgently. Mean follow-up was 7388 aneurysm-years. The most common was middle cerebral artery (MCA) aneurysms (535 aneurysms, 27.3%), followed by internal carotid artery (ICA) aneurysms not connected to the origin of the posterior communicating artery (PCom; 525 aneurysms, 26.8%). Aneurysms at the origin of the PCom were the third most common (401 aneurysms, 20.5%), followed by vertebral artery–basilar artery aneurysms (169 aneurysms, 8.6%). Fifty-six aneurysms ruptured during the follow-up period, with an overall annual incidence SAH of 0.76%. Mean duration to rupture from initial presentation was 547 days. Regarding the rupture risk factors, aneurysm size, specific location, history of SAH, and the presence of a daughter sac were found to be independent risk factors in both single and multivariate Cox proportional-hazard models. On the other hand, and surprisingly, smoking, family history of SAH, age, female sex, hypertension, and diabetes mellitus were not associated with risk of rupture. Average rupture size was 7.5 ± 5.74 mm. Of note, 39 ruptures (69.6%) occurred in aneurysms <7 mm in size. The probability of rupture increased with size. The authors then performed multiple analyses with the cutoff size set at 5, 6, 7, 8, 9, and 10 mm. They noted a statistical significance in all selected cutoff sizes with and without adjustment for other risk factors. In terms of locations, vertebrobasilar aneurysms were associated with the highest rupture risk, followed by PCom, MCA, anterior cerebral artery (ACA), and then finally ICA aneurysms. Vertebrobasilar and PCom aneurysms had a significantly higher hazard ratio of rupture, whereas MCA and ACA aneurysms had only a moderate increase in risk. Fifteen of the 56 aneurysm ruptures (26.8%) resulted in death, and 16 of the 56 (28.65) ended in moderate to severe disability (modified Rankin Scale score of 3-5). Fewer than half of the patients with ruptures returned to normal life. None of the patients who had large or giant aneurysms recovered without deficits. The mortality rate of these patients was 69% (9 of 13), whereas the mortality rate of aneurysms <5 mm was 18% (4 of 22).

This study confirms many concepts about intracranial aneurysms. More than half of the ruptured aneurysms ended in at least moderate disability, further revealing the devastating effect of aneurysmal SAH. Size and location have again been shown to be independent risk factors for rupture. Unlike ISUIA, however, this study showed what was suspected all along: that even small aneurysms rupture. Although the authors are to be commended for their efforts, this study has obvious limitations. First, there is a clear selection bias. Aneurysms suspected to be of high risk of rupture were treated outside of this cohort, which would explain the low incidence of SAH in their population. These include irregular aneurysms and aneurysms that presented with mass effect. In terms of risk factors, some findings replicated what has been previously published in the literature (eg, size, location, daughter sac, and history of SAH). Other conclusions failed to corroborate findings from other studies (eg, smoking, hypertension). Although this could be due to selection bias or small population size, it could also be explained by the variability in aneurysm natural history and further highlights our lack of understanding of the pathology.Although statistics generated by large-scale studies help us to better understand diseases, it should be noted that they apply for the general masses and give a global perspective and therefore have little implication for an individual in the clinic. This is particularly an issue when the number of variables increases such as in the case of aneurysms. As an example, a patient with a connective tissue disease with a 5-mm ACA aneurysm might be at a higher risk than an otherwise healthy patient with a 9-mm MCA aneurysm. When other variables such as age, aneurysm growth, shape, smoking, and SAH history are factored in, the complexity increases exponentially. In addition, aneurysm formation risk factors are not necessarily the same as rupture risk factors. In an ideal world, mathematically generated individualized risk assessment models would assist in decision-making and treatment algorithms. At this point in time, however, such a model remains out of immediate and practical reach. Further studies are required to improve our understanding of aneurysms on multiple levels, including clinical, biological, and mechanical 24).

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