Intracranial Aneurysms in Sickle Cell Disease

Author(s): Ramazan Jabbarli*, Thiemo F. Dinger, Daniela Pierscianek, Marvin D. Oppong, Bixia Chen, Philipp Dammann, Karsten H. Wrede, Klaus Kaier, Martin Köhrmann, Michael Forsting, Christoph Kleinschnitz, Ulrich Sure

Journal Name: Current Neurovascular Research

Volume 16 , Issue 1 , 2019

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Background: The exact causes of intracranial aneurysms (IAs) are still unknown. However, certain diseases are known to be associated with IAs.

Objective: To analyze the differences in IA characteristics in the general population and in individuals with sickle-cell disease (SCD).

Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library for Data on SCD patients with IAs. We compared IA characteristics of SCD patients with those from 2451 healthy IA carriers from our observational cohort.

Results: 129 SCD patients with IAs were identified in 42 studies. The SCD patient cohort was characterized by younger age (mean 27.1 vs 54.9 years, p<0.0001) and lower female prevalence (57.7% vs 68.4%, p=0.0177). The prevalence (47% vs 34.5%, p=0.004) and the number (3.02 vs 2.56 IAs/patient, p=0.004) of multiple IAs were also higher in the SCD cohort. Unruptured IAs (3.27 vs 6.16 mm, p<0.0001), but not ruptured IAs (7.8 vs 7.34 mm, p=0.9086) were significantly smaller in the SCD cohort. In addition, IAs were more frequently located in the internal carotid artery (45% vs 29%, p<0.0001) or posterior circulation (43% vs 20%, p<0.0001). Higher age (≥30 years, p=0.007), IA size ≥7 mm (p=0.008), and location in posterior circulation (p=0.01) were independently associated with subarachnoid hemorrhage in SCD.

Conclusion: There is a distinct demographic and radiographic pattern of IA in SCD. Risk factors for IA rupture in SCD are mostly congruent with those in healthy individuals.

Keywords: Intracranial aneurysm, subarachnoid hemorrhage, risk factors, sickle-cell disease, rupture, growth.

Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: A systematic review and meta-analysis. Lancet Neurol 2011; 10(7): 626-36.
Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: A guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke 2012; 43(6): 1711-37.
Brown RD Jr, Broderick JP. Unruptured intracranial aneurysms: epidemiology, natural history, management options, and familial screening. Lancet Neurol 2014; 13(4): 393-404.
Anson JA, Koshy M, Ferguson L, Crowell RM. Subarachnoid hemorrhage in sickle-cell disease. J Neurosurg 1991; 75(4): 552-8.
Preul MC, Cendes F, Just N, Mohr G. Intracranial aneurysms and sickle cell anemia: Multiplicity and propensity for the vertebrobasilar territory. Neurosurgery 1998; 42(5): 971-7. discussion 977-8
Brandao RA, de Carvalho GT, Reis BL, Bahia E, de Souza AA. Intracranial aneurysms in sickle cell patients: Report of 2 cases and review of the literature. Surg Neurol 2009; 72(3): 296-9. discussion 9.
Birkeland P, Gardner K, Kesse-Adu R, et al. Intracranial aneurysms in sickle-cell disease are associated with the hemoglobin ss genotype but not with moyamoya syndrome. Stroke 2016; 47(7): 1710-3.
Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med 2017; 376(16): 1561-73.
Dutta G, Sachdeva D, Singh D, Singh H, Srivastava AK. Mechanical versus electrical detachment of coils in treatment of intracranial aneurysms: Role in sickle cell disease. Neurol Neurochir Polska 2018; 52(6): 759-61.
Albanese E, Russo A, Ulm AJ. Fenestrated vertebrobasilar junction aneurysm: Diagnostic and therapeutic considerations. J Neurosurg 2009; 110(3): 525-9.
Balkaran B, Char G, Morris JS, Thomas PW, Serjeant BE, Serjeant GR. Stroke in a cohort of patients with homozygous sickle cell disease. J Pediatr 1992; 120(3): 360-6.
Batjer HH, Adamson TE, Bowman GW. Sickle cell disease and aneurysmal subarachnoid hemorrhage. Surg Neurol 1991; 36(2): 145-9.
Buonanno FS, Schmahmann JD, Romero JM, Makar RS. Case records of the massachusetts general hospital. Case 10-2016. A 22-year-old man with sickle cell disease, headache, and difficulty speaking. N Engl J Med 2016; 374(13): 1265-75.
Caprioli J, Fagadau W, Lesser R. Acute monocular visual loss secondary to anterior communicating artery aneurysm in a patient with sickle cell disease. Ann Ophthalmol 1983; 15(9): 873-6.
Chalif DJ, Decker RE. Intracranial aneurysms in sickle-cell anemia. J Neurosurg 1992; 76(6): 1051-2.
Cheatham ML, Brackett CE. Problems in management of subarachnoid hemorrhage in sickle cell anemia. J Neurosurg 1965; 23(5): 488-93.
Close RA, Buchheit WA. The management of ruptured intracranial aneurysm in sickle cell anemia. Case report. J Neurosurg 1977; 47(5): 761-5.
de los Reyes RA, Kantrowitz AB, Detwiler PW, Feghale JG, Hall CD, Sonstein WJ. Transoral-transclival clipping of a giant lower basilar artery aneurysm. Surg Neurol 1992; 38(5): 379-82.
Diggs LW, Brookoff D. Multiple cerebral aneurysms in patients with sickle cell disease. South Med J 1993; 86(4): 377-9.
Dmytriw AA, Martinez JL, Marotta T, Montanera W, Cusimano M, Bharatha A. Use of a flow-diverting stent for ruptured dissecting aneurysm treatment in a patient with sickle cell disease. Interv Neuroradiol 2016; 22(2): 143-7.
Ediriwickrema A, Williamson T, Hebert R, Matouk C, Johnson MH, Bulsara KR. Intracranial stenting as monotherapy in subarachnoid hemorrhage and sickle cell disease. J Neurointerv Surg 2013; 5(2): e4.
Firth PG, Peterfreund RA. Management of multiple intracranial aneurysms: Neuroanesthetic considerations of sickle cell disease. J Neurosurg Anesthesiol 2000; 12(4): 366-71.
Fulkerson DH, Voorhies JM, Payner TD, et al. Middle cerebral artery aneurysms in children: Case series and review. J Neurosurg Pediatr 2011; 8(1): 79-89.
Ganesalingam J, Redwood R, Jenkins I. Thrombolysis of an acute stroke presentation with an incidental unruptured aneurysm. JRSM Cardiovasc Dis 2013; 2: 2048004013478808.
Greer M, Schotland D. Abnormal hemoglobin as a cause of neurologic disease. Neurology 1962; 12: 114-23.
Gross BA, Smith ER, Scott RM, Orbach DB. Intracranial aneurysms in the youngest patients: Characteristics and treatment challenges. Pediatr Neurosurg 2015; 50(1): 18-25.
Hitchcock ER, Tsementzis SA, Richardson SG, Turner J. Subarachnoid hemorrhage in sickle-cell anemia. Surg Neurol 1983; 19(3): 251-4.
Huang J, McGirt MJ, Gailloud P, Tamargo RJ. Intracranial aneurysms in the pediatric population: Case series and literature review. Surg Neurol 2005; 63(5): 424-32.
Kassim AA, Pruthi S, Day M, et al. Silent cerebral infarcts and cerebral aneurysms are prevalent in adults with sickle cell anemia. Blood 2016; 127(16): 2038-40.
Kossorotoff M, Brousse V, Grevent D, et al. Cerebral haemorrhagic risk in children with sickle-cell disease. Dev Med Child Neurol 2015; 57(2): 187-93.
Lasjaunias P, Wuppalapati S, Alvarez H, Rodesch G, Ozanne A. Intracranial aneurysms in children aged under 15 years: Review of 59 consecutive children with 75 aneurysms. Childs Nerv Syst 2005; 21(6): 437-50.
Liaquat I, Murphy M, Bassi S, Bullock PR. Paediatric and adult vascular intracranial complications of sickle-cell disease. Acta Neurochir (Wien) 2010; 152(7): 1175-9.
Love LC, Mickle JP, Sypert GW. Ruptured intracranial aneurysms in cases of sickle cell anemia. Neurosurgery 1985; 16(6): 808-12.
Lyon M, Jeter J, Lottenberg R. Approach to the diagnosis and treatment of acute subarachnoid hemorrhage in a patient with sickle cell disease. Am J Emerg Med 2015; 33(3): 481e3. 4
McQuaker IG, Jaspan T, McConachie NS, Dolan G. Coil embolization of cerebral aneurysms in patients with sickling disorders. Br J Haematol 1999; 106(2): 388-90.
Nabavizadeh SA, Vossough A, Ichord RN, et al. Intracranial aneurysms in sickle cell anemia: Clinical and imaging findings. J Neurointerv Surg 2016; 8(4): 434-40.
Overby MC, Rothman AS. Multiple intracranial aneurysms in sickle cell anemia. Report of two cases. J Neurosurg 1985; 62(3): 430-4.
Oyesiku NM, Barrow DL, Eckman JR, Tindall SC, Colohan AR. Intracranial aneurysms in sickle-cell anemia: Clinical features and pathogenesis. J Neurosurg 1991; 75(3): 356-63.
Powars D, Wilson B, Imbus C, Pegelow C, Allen J. The natural history of stroke in sickle cell disease. Am J Med 1978; 65(3): 461-71.
Rinnert S, Scalea T, Sinert R. Management of nontraumatic subarachnoid hemorrhage in a patient with sickle-cell disease: a case report. Acad Emerg Med 1996; 3(9): 859-63.
Rupp C, Riggs HE. Clinical pathologic conference. Neurology 1953; 3(10): 779-82.
Saini S, Speller-Brown B, Wyse E, et al. Unruptured intracranial aneurysms in children with sickle cell disease: Analysis of 18 aneurysms in 5 patients. Neurosurgery 2015; 76(5): 531-8.
Sampson I, Pratila M, Pratilas V. Anesthetic management of cerebral aneurysmectomy in a sickle cell anemia patient. Mount Sinai J Med (New York) 1982; 49(4): 326-8.
Scully RE, Mark EJ, McNelly BU. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 52-1983. Pulmonary hypertension associated with abnormal hemoglobin. N Engl J Med 1983; 309(26): 1627-36.
Vicari P, Choairy AC, Siufi GC, Arantes AM, Fonseca JR, Figueiredo MS. Embolization of intracranial aneurysms and sickle cell disease. Am J Hematol 2004; 76(1): 83-4.
Wertham F, Mitchell N, Angrist A. The brain in sickle cell anemia. Arch Neur Psych 1942; 47(5): 752-67.
Wiznitzer M, Berman B. Subarachnoid hemorrhage in sickle cell anemia: Evaluation using parenchymal and vascular magnetic resonance imaging. Neurology 1991; 41(9): 1521-2.
Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet 2010; 376(9757): 2018-31.
Hebbel RP. Ischemia-reperfusion injury in sickle cell anemia: Relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain. Hematol Oncol Clin North Am 2014; 28(2): 181-98.
Frosen J, Tulamo R, Paetau A, et al. Saccular intracranial aneurysm: Pathology and mechanisms. Acta Neuropathol 2012; 123(6): 773-86.
Turjman AS, Turjman F, Edelman ER. Role of fluid dynamics and inflammation in intracranial aneurysm formation. Circulation 2014; 129(3): 373-82.
Cebral JR, Raschi M. Suggested connections between risk factors of intracranial aneurysms: A review. Ann Biomed Eng 2013; 41(7): 1366-83.
Jabbarli R, Dinger TF, Oppong MD, et al. Risk factors for and clinical consequences of multiple intracranial aneurysms: A systematic review and meta-analysis. Stroke 2018; 49(4): 848-55.

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Article Details

Year: 2019
Published on: 31 January, 2019
Page: [63 - 76]
Pages: 14
DOI: 10.2174/1567202616666190131160847
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