Category Archives: Vascular

Ophthalmic artery aneurysm surgery

Ophthalmic artery aneurysm surgery

The ophthalmic artery aneurysms can treated safe and effective through a frontolateral approach 1).

The most important risk associated with clipping ophthalmic artery aneurysms is a new visual deficit. Meticulous microsurgical technique is necessary during anterior clinoidectomy, aneurysm dissection, and clip application to optimize visual outcomes, and aggressive medical management postoperatively might potentially decrease the incidence of delayed visual deficits. As the results of endovascular therapy and specifically flow diverters become known, they warrant comparison with these surgical benchmarks to determine best practices 2).

For ophthalmic artery aneurysm treatment if necessary, the ophthalmic artery may be sacrificed without worsening of vision in the vast majority.

Surgery is technically demanding because these aneurysms are often large and may extend into the cavernous sinus 3) 4) 5) 6) 7) 8).

Care must be taken to avoid optic nerve injury caused by the retraction and/or the heat of the drill 9).

For unruptured intracranial aneurysm, drill off anterior clinoid process via an extradural approach before opening dura to approach aneurysm neck maybe safe. Not for ruptured.

Cutting the falciform ligament early decompresses the optic nerve, and helps minimize worsening of visual impairment from surgical manipulation.

In most cases, a side angled clip can be placed paralell to the parent artery along the neck of the aneurysm 10).

Contralateral approach

Case series

2018

Kamide et al. retrospectively reviewed results from microsurgical clipping of 208 OphA aneurysms in 198 patients.

Patient demographics, aneurysm morphology, clinical characteristics, and patient outcomes were recorded and analyzed.

Despite 20% of these aneurysms being large or giant in size, complete aneurysm occlusion was accomplished in 91% of 208 cases, with OphA patency preserved in 99.5%. The aneurysm recurrence rate was 3.1% and the retreatment rate was 0%.

Good outcomes (modified Rankin Scale score 0-2) were observed in 96.2% of patients overall and in all 156 patients with unruptured aneurysms. New visual field defects (hemianopsia or quadrantanopsia) were observed in 8 patients (3.8%), decreased visual acuity in 5 (2.4%), and monocular blindness in 9 (4.3%). Vision improved in 9 (52.9%) of the 17 patients with preoperative visual deficits.

The most important risk associated with clipping OphA aneurysms is a new visual deficit. Meticulous microsurgical technique is necessary during anterior clinoidectomy, aneurysm dissection, and clip application to optimize visual outcomes, and aggressive medical management postoperatively might potentially decrease the incidence of delayed visual deficits. As the results of endovascular therapy and specifically flow diverters become known, they warrant comparison with these surgical benchmarks to determine best practices 11).

2017

The clinical data of 95 patients with carotid ophthalmic artery aneurysms treated via frontolateral approach in the last 1.5 years in Beijing Tiantan Hospital and Beijing Anzhen Hospital were analyzed retrospectively.Before the operation, digital subtraction angiogram (DSA) was performed among all patients.The patients were divided into two groups by the lateral approach.According to preoperative classification, surgical characteristics and prognosis were summarized.

Ninety-five cases of ophthalmic aneurysms were divided into type Ⅰ of 44 cases (46.3%), type Ⅱ of 34 cases (35.7%) and type Ⅲ of 17cases (17.9%), according to the results of DSA.The diameter of aneurysm was <10 mm (35 cases), 10-25 mm (34 cases), and >25 mm (26 cases). In the 17 cases of subarachnoid hemorrhage (SAH), 8 cases were ruptured carotid-ophthalmic artery aneurysms.Among those 95 patients, 93 were clipped successfully, 2 was trapped.Multiple aneurysms in 5 cases were treated in one surgical session through the same approach.No aneurysm residual was found after postoperative CTA review.Ipsilateral vision of 3 cases were decline.Cerebral infarction was appeared in 9 cases.All the others had a good recovery.

The carotid-ophthalmic artery aneurysms could be well exposed. Microsurgery through frontolateral approach has the advantages such as minimal invasion, less effect on the patients’ look and simple procedure.The frontolateral approach is safe and effective in surgery for ophthalmic segment of the internal carotid artery aneurysms 12).

Case reports

Rustemi et al. illustrated the first case of indocyanine green videoangiography (ICG-VA) application in an optic penetrating ophthalmic artery aneurysm treatment. A 57-year-old woman presented with temporal hemianopsia, slight right visual acuity deficit, and new onset of headache. The cerebral angiography detected a right ophthalmic artery aneurysm medially and superiorly projecting. The A1 tract of the ipsilateral anterior cerebral artery was elevated and curved, being suspicious for an under optic aneurysm growth. Surgery was performed. Initially the aneurysm was not visible. ICG-VA permitted the transoptic aneurysm visualization. After optic canal opening, the aneurysm was clipped and transoptic ICG-VA confirmed the aneurysm occlusion. ICG-VA showed also the slight improvement of the optic nerve pial vascularization. Postoperatively, the visual acuity was 10/10 and the hemianopsia did not worsen.

The elevation and curve of the A1 tract in medially and superiorly projecting ophthalmic aneurysms may be an indirect sign of under optic growth, or optic splitting aneurysms. ICG-VA transoptic aneurysm detection and occlusion confirmation reduces the surgical maneuvers on the optic nerve, contributing to function preservation 13).

1) , 12)

Wang JT, Kan ZS, Wang S. [Surgical management of ophthalmic artery aneurysms via minimally invasive frontolateral approach]. Zhonghua Yi Xue Za Zhi. 2017 Apr 18;97(15):1179-1183. doi: 10.3760/cma.j.issn.0376-2491.2017.15.014. Chinese. PubMed PMID: 28427127.
2) , 11)

Kamide T, Tabani H, Safaee MM, Burkhardt JK, Lawton MT. Microsurgical clipping of ophthalmic artery aneurysms: surgical results and visual outcomes with 208 aneurysms. J Neurosurg. 2018 Jan 26:1-11. doi: 10.3171/2017.7.JNS17673. [Epub ahead of print] PubMed PMID: 29372879.
3)

Hosobuchi Y. Direct surgical treatment of giant intracranial aneurysms. J Neurosurg. 1979;51(6):743–756.
4)

Sundt T M Jr, Piepgras D G. Surgical approach to giant intracranial aneurysms. Operative experience with 80 cases. J Neurosurg. 1979;51(6):731–742.
5)

Almeida G M, Shibata M K, Bianco E. Carotid-ophthalmic aneurysms. Surg Neurol. 1976;5(1):41–45.
6)

Kattner K A, Bailes J, Fukushima T. Direct surgical management of large bulbous and giant aneurysms involving the paraclinoid segment of the internal carotid artery: report of 29 cases. Surg Neurol. 1998;49(5):471–480.
7)

Nutik S L. Ventral paraclinoid carotid aneurysms. J Neurosurg. 1988;69(3):340–344.
8)

Nutik S. Carotid paraclinoid aneurysms with intradural origin and intracavernous location. J Neurosurg. 1978;48(4):526–533
9)

Kumon Y, Sakaki S, Kohno K, Ohta S, Ohue S, Oka Y. Asymptomatic, unruptured carotid-ophthalmic artery aneurysms: angiographical differentiation of each type, operative results, and indications. Surg Neurol. 1997 Nov;48(5):465-72. PubMed PMID: 9352810.
10)

Day AL. Clinicoanatomic features of supraclinoid aneurysms. Clin Neurosurg. 1990;36:256-74. Review. PubMed PMID: 2403885.
13)

Rustemi O, Cester G, Causin F, Scienza R, Della Puppa A. Indocyanine Green Videoangiography Transoptic Visualization and Clipping Confirmation of an Optic Splitting Ophthalmic Artery Aneurysm. World Neurosurg. 2016 Jun;90:705.e5-705.e8. doi: 10.1016/j.wneu.2016.03.010. Epub 2016 Mar 12. PubMed PMID: 26979923.

Update: Unruptured intracranial aneurysm treatment score

Unruptured intracranial aneurysm treatment score

see also PHASES score.

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

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

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

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

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


A tertiary center with focus on vascular neurosurgery, aimed to investigate whether there treatment decision-making in patients with UIA has been in accordance with the published UIATS. A retrospective analysis of patients admitted to the center with UIA was performed. UIATS was applied to all identified UIA. Three decision groups were defined: (a) UIATS favoring treatment, (b) UIATS favoring observation, and © UIATS inconclusive. These results were then compared to our clinical decisions. Spearman’s rank-order correlation (ρ) was run to determine the relationship between the UIATS and our clinical decisions. Cases of discrepancies between UIATS and our clinical decisions were then examined for complications, defined as periprocedural adverse events in treated aneurysms, or aneurysm rupture in untreated aneurysms. Ninety-three patients with 147 UIA were included. A total of 118/147 (80.3%) UIA were treated. In 70/118 (59.3%), UIATS favored treatment, in 18/118 (15.3%), it was inconclusive, and in 30/118 (25.4%), it favored observation. A total of 29/147 (19.7%) UIA were not treated. In 15/29 (51.7%), UIATS favored observation, in 9/29 (31%), it favored treatment, and in 5/29 (17.2%), it was inconclusive (ρ = 0.366, p < 0.01). Discrepancies between UIATS and our clinical decisions did not correlate with complications (ρ = 0.034, p = 0.714). Our analysis shows that our more intuitive clinical decision-making has been in line with UIATS. Our treatment decisions did not correlate with an increased rate of complications 2).


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

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

Compared with the authors’ experience, the UIATS recommended overtreatment of UIAs. Although the UIATS could be used as a screening tool, individualized treatment recommendations based on consultation with a cerebrovascular specialist are necessary. Further validation with longitudinal data on rupture rates of UIAs is needed before widespread use 3).

1)

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

Hernández-Durán S, Mielke D, Rohde V, Malinova V. The application of the unruptured intracranial aneurysm treatment score: a retrospective, single-center study. Neurosurg Rev. 2018 Feb 1. doi: 10.1007/s10143-018-0944-2. [Epub ahead of print] PubMed PMID: 29388120.
3)

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

NeuroEndovascular Challenges: Frontiers in Neurosurgery Volume 1

NeuroEndovascular Challenges: Frontiers in Neurosurgery Volume 1

by Simone Peschillo

List Price: $94.00

ADD TO SHOPPING CART

Remarkable advances have been made in embolization of cerebral aneurysms, arteriovenous malformations and stroke treatment during the past decades. Endovascular techniques are less invasive than other forms of neurosurgery. However, endovascular neurosurgery is becoming more complicated as the technology is becoming more sophisticated. Frontiers in Neurosurgery is an ebook series which triggers principle issues that still fuel debate in neurosurgery. The series is intended as a reference for practicing endovascular neurosurgeons, vascular neurosurgeons, interventional neurologists and neuroradiologists who have a solid knowledge of neuroangiography. The first volume of this series brings reviews on a variety of challenges that neuroendovascular surgeons can face such as: – Devices for Neuroendovascular Treatment – Dual Antiplatelet Therapy in Neuroendovascular Procedures – Endovascular Reperfusion Management for Acute Ischemic Stroke – Spinal Vascular Pathology – Anesthesia Options for Endovascular Neurosurgery … and much more.

Update: Abciximab

Abciximab

Abciximab is made from the Fab fragments of an immunoglobulin that targets the glycoprotein IIbIIIa receptor on the platelet membrane.

Abciximab (previously known as c7E3 Fab), a glycoprotein IIb/IIIa receptor antagonist manufactured by Janssen Biologics BV and distributed by Eli Lilly under the trade name ReoPro, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures like angioplasty to prevent platelets from sticking together and causing thrombus (blood clot) formation within the coronary artery. It is a glycoprotein IIb/IIIa inhibitor.

While abciximab has a short plasma half-life, due to its strong affinity for its receptor on the platelets, it may occupy some receptors for weeks. In practice, platelet aggregation gradually returns to normal about 96 to 120 hours after discontinuation of the drug 1).

Rx: 0.25 mg/kg IV bolus over at least 1 min, 10-60 min before start of PCI, THEN

0.125 mcg/kg/min IV continuous infusion for 12 hr; not to exceed infusion rate of 10 mcg/min


Patel et al. evaluated the efficacy of treatment of acute thrombus formation with abciximab, as well as the results of pre-procedure platelet inhibition testing.

Acute thrombus formation was encountered in five patients following PED placement (5%). Early angiographic signs were present in all cases and included progressive stagnation of blood flow in covered side branches, occlusion of covered side branches, excessive stagnation of blood flow in the target aneurysm, as well as occlusion of the target aneurysm. These sequelae completely resolved following abciximab treatment in all five cases, with no permanent neurological morbidity or mortality. Four of the five patients had a pre-procedure P2Y12 value >200 (range 201-227).

Progressive stagnation or occlusion of covered side branches or target aneurysm are early angiographic signs of acute thrombus formation following PED placement and should prompt immediate treatment with a glycoprotein IIb/IIIa inhibitor. Platelet inhibition testing may help identify those patients who are at an increased risk for this complication 2).


A review provides a comprehensive evaluation of the current published literature pertaining to the use of all available GP IIb/IIIa inhibitors for thromboembolic complications, providing recommendations for dosing and administration of abciximab, eptifibatide, and tirofiban based on previously published rates of efficacy and intracranial hemorrhage 3).


Abciximab produces a high rate of angiographic improvement and a low incidence of postprocedural infarct in neuroendovascular procedures complicated by thromboemboli. IA abciximab produces greater angiographic improvement than IV treatment. Postprocedural infarction is less common in patients with complete angiographic response than in those with partial or no response 4).


In acute ICA-MCA/distal ICA occlusions, extracranial stenting followed by intracranial IA Abciximab and thrombectomy appears feasible, effective, and safe. Further evaluation of this treatment strategy is warranted 5).


There was no statistically significant difference in the rate of ischemic stroke or postprocedural hemorrhage with the use of abciximab compared with the use of eptifibatide in treatment of intraprocedural thrombosis 6).

1)

Tanguay, J.F., Eur Heart J 1999; 1 (suppl E): E27-E35
2)

Patel A, Miller TR, Shivashankar R, Jindal G, Gandhi D. Early angiographic signs of acute thrombus formation following cerebral aneurysm treatment with the Pipeline embolization device. J Neurointerv Surg. 2017 Nov;9(11):1125-1130. doi: 10.1136/neurintsurg-2016-012701. Epub 2016 Oct 21. PubMed PMID: 27770038.
3)

Dornbos D 3rd, Katz JS, Youssef P, Powers CJ, Nimjee SM. Glycoprotein IIb/IIIa Inhibitors in Prevention and Rescue Treatment of Thromboembolic Complications During Endovascular Embolization of Intracranial Aneurysms. Neurosurgery. 2017 May 3. doi: 10.1093/neuros/nyx170. [Epub ahead of print] PubMed PMID: 28472526.
4)

Kansagra AP, McEachern JD, Madaelil TP, Wallace AN, Cross DT 3rd, Moran CJ, Derdeyn CP. Intra-arterial versus intravenous abciximab therapy for thromboembolic complications of neuroendovascular procedures: case review and meta-analysis. J Neurointerv Surg. 2017 Feb;9(2):131-136. doi: 10.1136/neurintsurg-2016-012587. Epub 2016 Aug 18. PubMed PMID: 27540089.
5)

Al-Mufti F, Amuluru K, Manning NW, Khan I, Peeling L, Gandhi CD, Prestigiacomo CJ, Pushchinska G, Fiorella D, Woo HH. Emergent carotid stenting and intra-arterial abciximab in acute ischemic stroke due to tandem occlusion. Br J Neurosurg. 2017 Oct;31(5):573-579. doi: 10.1080/02688697.2017.1297377. Epub 2017 Mar 15. PubMed PMID: 28298139.
6)

Adeeb N, Griessenauer CJ, Moore JM, Foreman PM, Shallwani H, Motiei-Langroudi R, Gupta R, Baccin CE, Alturki A, Harrigan MR, Siddiqui AH, Levy EI, Ogilvy CS, Thomas AJ. Ischemic Stroke After Treatment of Intraprocedural Thrombosis During Stent-Assisted Coiling and Flow Diversion. Stroke. 2017 Apr;48(4):1098-1100. doi: 10.1161/STROKEAHA.116.016521. Epub 2017 Feb 28. PubMed PMID: 28246277.

Update: Familial cerebral cavernous malformation

Familial cerebral cavernous malformation

Familial cerebral cavernous malformations, which account for at least 20% of all cases, can be passed from parent to child. Individuals with familial CCMs typically have multiple lesions. Familial CCMs are passed through families in an autosomal dominant manner, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Each child of an individual with familial CCM has a 50% chance of inheriting the mutation.

It is an autosomal-dominant disease with incomplete penetrance. The pathogenic genes of FCCM have been mapped into three loci: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10.

see https://www.ncbi.nlm.nih.gov/books/NBK1293/.


Although the clinical course is unpredictable, symptoms typically present during adult life and include headaches, focal neurological deficits, seizures, and potentially fatal stroke. In addition to neural lesions, extraneural cavernous malformations have been described in familial disease in several tissues, in particular the skin 1).


In recent years there has been an increasing amount of publications linking FCCMs with other pathology, predominantly with extracranial and intracranial mesenchymal anomalies.

When faced with an unusual clinical feature in a patient with a Mendelian disorder, the clinician may entertain the possibilities of either the feature representing a novel manifestation of that disorder or the co-existence of a different inherited condition. Here we describe an individual with a submandibular oncocytoma, pulmonary bullae and renal cysts as well as multiple cerebral cavernous malformations and haemangiomas. Genetic investigations revealed constitutional mutations in FLCN, associated with Birt-Hogg-Dubé syndrome (BHD) and CCM2, associated with familial cerebral cavernous malformation. Intracranial vascular pathologies (but not cerebral cavernous malformation) have recently been described in a number of individuals with BHD (Kapoor et al. in Fam Cancer 14:595-597, 10.1007/s10689-015-9807-y , 2015) but it is not yet clear whether they represent a genuine part of that conditions’ phenotypic spectrum. We suggest that in such instances of potentially novel clinical features, more extensive genetic testing to consider co-existing conditions should be considered where available. The increased use of next generation sequencing applications in diagnostic settings is likely to lead more cases such as this being revealed 2).


A study described an unusual association between 2 independent hereditary diseases of confirmed genetic origin-a combination that has not been described previously 3).

Rosário Marques et al. documented a novel mutation on KRIT1 gene, and the second to be reported in a Portuguese family. This mutation consists in a two nucleotide insertion (c.947_948insAC) within the exon 10, resulting in premature protein termination (p.Leu317Argfs*2). These findings will hopefully contribute to a better clinical, imaging and genetic characterisation of this disease, particularly while trying to identify the factors that influence its treatment and prognosis 4).


Yang et al., investigated the genetic mutation in a Chinese family with FCCM.

The proband is a 29-year-old female presenting with a 1-month history of headache. Brain magnetic resonance imaging (MRI) revealed multiple intracranial lesions, the largest one showing a popcorn-like appearance. After a 4-year conservative observation, there was no significant clinical or radiological progression. Family investigation found five of her relatives had multiple CCM lesions. DNA sequencing analysis in the proband disclosed a novel heterozygous deletion mutation (c.1919delT; p.Phe640SerfsX21) in exon 17 of the CCM1/KRIT1 gene. This mutation leads to a frameshift and is predicted to cause a premature termination codon to generate a truncated Krev interaction trapped-1 (Krit1) protein of 659 amino acids. The mutation segregated with the disease in the family. C The current study identified a novel CCM1/KRIT1 heterozygous deletion mutation (c.1919delT) associated with FCCM. The findings expand the CCM gene mutation profiles in the Chinese population, which will be beneficial for genetic counseling 5).


A proband was hospitalized for sudden unconsciousness and underwent surgical treatment. The section of lesions showed classical cavernous-dilated vessels without intervening brain parenchyma, and hemosiderin-laden macrophages were accumulated in the surrounding tissue. In addition, magnetic resonance imaging (MRI) showed severe multiple cerebral cavernous malformation (CCM) lesions in cerebrum, brainstem, and cerebellum in other affected subjects. Especially, for the proband’s mother, hundreds of lesions were presented, and a few lesions were found in the expanded lateral ventricle (Evans’ index =0.33). Moreover, she showed the similar symptoms of hydrocephalus, including headache, dizziness, and diplopia. It was extremely rare in previous reports. To date, the genetic alterations leading to FCCM in Chinese population remain largely unknown. We investigated genetic defects of this family. Sequence analyses disclosed a novel heterozygous insertion mutation (c.1896_1897insT; p.Pro633SerfsTer22) in KRIT1/CCM1. Moreover, our real-time PCR results revealed that the mRNA level of KRIT1/CCM1 were significantly decreased in FCCM subjects (CCM family =0.42 ± 0.20 vs. healthy control =1.01 ± 0.16, P = 0.004). It indicated that this mutation could cause KRIT1/CCM1 functional mRNA deficiency. It may be closely related with the pathogenesis of FCCM. Our findings provided a new gene mutation profile which will be of great significance in early diagnosis and appropriate clinical surveillance of FCCM patients 6).

Case series

Fifty-seven familial CCM type-1 patients were included in this institutional review board-approved study. Baseline SWI (n = 57) and follow-up SWI (n = 17) were performed on a 3T Siemens MR scanner with lesions counted manually by the study neuroradiologist. We modified an algorithm for detecting radiation-induced microbleeds on SWI images in brain tumor patients, using a training set of 22 manually delineated CCM microbleeds from two random scans. Manual and automated counts were compared using linear regression with robust standard errors, intra-class correlation (ICC), and paired t tests. A validation analysis comparing the automated counting algorithm and a consensus read from two neuroradiologists was used to calculate sensitivity, the proportion of microbleeds correctly identified by the automated algorithm. RESULTS: Automated and manual microbleed counts were in strong agreement in both baseline (ICC = 0.95, p < 0.001) and longitudinal (ICC = 0.88, p < 0.001) analyses, with no significant difference between average counts (baseline p = 0.11, longitudinal p = 0.29). In the validation analysis, the algorithm correctly identified 662 of 1325 microbleeds (sensitivity=50%), again with strong agreement between approaches (ICC = 0.77, p < 0.001). CONCLUSION: The automated algorithm is a consistent method for counting microbleeds in familial CCM patients that can facilitate lesion quantification and tracking 7).


The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease 8).

1)

de Vos IJ, Vreeburg M, Koek GH, van Steensel MA. Review of familial cerebral cavernous malformations and report of seven additional families. Am J Med Genet A. 2017 Feb;173(2):338-351. doi: 10.1002/ajmg.a.38028. Epub 2016 Oct 28. Review. PubMed PMID: 27792856.
2)

Whitworth J, Stausbøl-Grøn B, Skytte AB. Genetically diagnosed Birt-Hogg-Dubé syndrome and familial cerebral cavernous malformations in the same individual: a case report. Fam Cancer. 2017 Jan;16(1):139-142. doi: 10.1007/s10689-016-9928-y. PubMed PMID: 27722904; PubMed Central PMCID: PMC5243871.
3)

Belousova OB, Okishev DN, Ignatova TM, Balashova MS, Boulygina ES. Hereditary Multiple Cerebral Cavernous Malformations Associated with Wilson Disease and Multiple Lipomatosis. World Neurosurg. 2017 Sep;105:1034.e1-1034.e6. doi: 10.1016/j.wneu.2017.06.002. Epub 2017 Jun 8. PubMed PMID: 28602929.
4)

Rosário Marques I, Antunes F, Ferreira N, Grunho M. Familial cerebral cavernous malformation: Report of a novel KRIT1 mutation in a Portuguese family. Seizure. 2017 Nov 10;53:72-74. doi: 10.1016/j.seizure.2017.10.020. [Epub ahead of print] PubMed PMID: 29145060.
5)

Yang C, Wu B, Zhong H, Li Y, Zheng X, Xu Y. A novel CCM1/KRIT1 heterozygous deletion mutation (c.1919delT) in a Chinese family with familial cerebral cavernous malformation. Clin Neurol Neurosurg. 2017 Nov 20;164:44-46. doi: 10.1016/j.clineuro.2017.11.005. [Epub ahead of print] PubMed PMID: 29169046.
6)

Wang H, Pan Y, Zhang Z, Li X, Xu Z, Suo Y, Li W, Wang Y. A Novel KRIT1/CCM1 Gene Insertion Mutation Associated with Cerebral Cavernous Malformations in a Chinese Family. J Mol Neurosci. 2017 Feb;61(2):221-226. doi: 10.1007/s12031-017-0881-5. Epub 2017 Feb 3. PubMed PMID: 28160210.
7)

Zou X, Hart BL, Mabray M, Bartlett MR, Bian W, Nelson J, Morrison LA, McCulloch CE, Hess CP, Lupo JM, Kim H. Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations. Neuroradiology. 2017 Jul;59(7):685-690. doi: 10.1007/s00234-017-1845-8. Epub 2017 May 22. PubMed PMID: 28534135; PubMed Central PMCID: PMC5501247.
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Strickland CD, Eberhardt SC, Bartlett MR, Nelson J, Kim H, Morrison LA, Hart BL. Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Radiology. 2017 Aug;284(2):443-450. doi: 10.1148/radiol.2017161127. Epub 2017 Mar 20. PubMed PMID: 28318403; PubMed Central PMCID: PMC5519414.