Natural history and imaging prevalence of cavernous malformations in children and young adults

Clinical article

View More View Less
  • 1 Departments of Neurosurgery and
  • | 2 Radiology, University of Michigan, Ann Arbor, Michigan
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Print or Print + Online Sign in

Object

This study was undertaken to define the age-related prevalence of cavernous malformations (CMs) in children and young adults undergoing intracranial imaging. In addition, the authors aim to clarify the natural history of CMs in young people, especially in those with incidentally discovered lesions.

Methods

To identify those patients with CMs, the authors retrospectively reviewed the electronic medical records of 14,936 consecutive patients 25 years of age or younger who had undergone brain MR imaging. In patients with a CM, clinical and imaging data were collected. Patients with untreated cavernomas who had more than 6 months of clinical and MR imaging follow-up were included in a natural history analysis. The natural history analysis included 110 CMs in 56 patients with a 3.5-year mean clinical follow-up interval (199 patient-years and 361 cavernoma-years).

Results

In 92 patients (0.6%), 164 CMs were identified. The imaging prevalence of cavernomas increased with advancing age (p = 0.002). Multiple CMs occurred in 28 patients (30%), and 8 patients (9%) had a family history of multiple CMs. Fifty patients (54%) presented with symptoms related to the cavernoma, of whom 30 presented with hemorrhage (33%). Of the 164 cavernomas identified, 103 (63%) were considered incidental, asymptomatic lesions. Larger size was associated with acute symptomatic presentation (p = 0.0001). During the follow-up interval, 6 patients with 8 cavernomas developed 11 symptomatic hemorrhages after initial identification. Five of the patients who had a hemorrhage during the follow-up interval had initially presented with hemorrhage, while only 1 had presented incidentally. The hemorrhage rate for all patients in the natural history group was 1.6% per patient-year and 0.9% per cavernoma-year. The hemorrhage rate was 8.0% per patient-year in the symptomatic group versus 0.2% in the incidental group. Symptomatic hemorrhage after long-term follow-up was associated with initial acute presentation (p = 0.02).

Conclusions

The imaging prevalence of CM increases with advancing age during childhood. Patients presenting without hemorrhage have a significantly lower risk of bleeding compared with those who present with acute neurological symptoms. Comparing this series of children to prior analyses of CM natural history in adults, the authors' data do not suggest a higher bleeding risk in younger patients.

Abbreviations used in this paper:

CM = cavernous malformation; DVA = developmental venous anomaly.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
  • 1

    Abdulrauf SI, , Kaynar MY, & Awad IA: A comparison of the clinical profile of cavernous malformations with and without associated venous malformations. Neurosurgery 44:4147, 1999

    • Search Google Scholar
    • Export Citation
  • 2

    Abla AA, , Lekovic GP, , Garrett M, , Wilson DA, , Nakaji P, & Bristol R, et al.: Cavernous malformations of the brainstem presenting in childhood: surgical experience in 40 patients. Neurosurgery 67:15891599, 2010

    • Search Google Scholar
    • Export Citation
  • 3

    Acciarri N, , Galassi E, , Giulioni M, , Pozzati E, , Grasso V, & Palandri G, et al.: Cavernous malformations of the central nervous system in the pediatric age group. Pediatr Neurosurg 45:81104, 2009

    • Search Google Scholar
    • Export Citation
  • 4

    Al-Shahi Salman R, , Berg MJ, , Morrison L, & Awad IA: Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Stroke 39:32223230, 2008

    • Search Google Scholar
    • Export Citation
  • 5

    Awad IA, , Robinson JR Jr, , Mohanty S, & Estes ML: Mixed vascular malformations of the brain: clinical and pathogenetic considerations. Neurosurgery 33:179188, 1993

    • Search Google Scholar
    • Export Citation
  • 6

    Barker FG II, , Amin-Hanjani S, , Butler WE, , Lyons S, , Ojemann RG, & Chapman PH, et al.: Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system. Neurosurgery 49:1525, 2001

    • Search Google Scholar
    • Export Citation
  • 7

    Batra S, , Lin D, , Recinos PF, , Zhang J, & Rigamonti D: Cavernous malformations: natural history, diagnosis and treatment. Nat Rev Neurol 5:659670, 2009

    • Search Google Scholar
    • Export Citation
  • 8

    Bertalanffy H, , Benes L, , Miyazawa T, , Alberti O, , Siegel AM, & Sure U: Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients. Neurosurg Rev 25:155, 2002

    • Search Google Scholar
    • Export Citation
  • 9

    Bhardwaj RD, , Auguste KI, , Kulkarni AV, , Dirks PB, , Drake JM, & Rutka JT: Management of pediatric brainstem cavernous malformations: experience over 20 years at the hospital for sick children. Clinical article. J Neurosurg Pediatr 4:458464, 2009

    • Search Google Scholar
    • Export Citation
  • 10

    Buckingham MJ, , Crone KR, , Ball WS, & Berger TS: Management of cerebral cavernous angiomas in children presenting with seizures. Childs Nerv Syst 5:347349, 1989

    • Search Google Scholar
    • Export Citation
  • 11

    Burn S, , Gunny R, , Phipps K, , Gaze M, & Hayward R: Incidence of cavernoma development in children after radiotherapy for brain tumors. J Neurosurg 106:5 Suppl 379383, 2007

    • Search Google Scholar
    • Export Citation
  • 12

    Cakirer S: De novo formation of a cavernous malformation of the brain in the presence of a developmental venous anomaly. Clin Radiol 58:251256, 2003

    • Search Google Scholar
    • Export Citation
  • 13

    Campeau NG, & Lane JI: De novo development of a lesion with the appearance of a cavernous malformation adjacent to an existing developmental venous anomaly. AJNR Am J Neuroradiol 26:156159, 2005

    • Search Google Scholar
    • Export Citation
  • 14

    Cantu C, , Murillo-Bonilla L, , Arauz A, , Higuera J, , Padilla J, & Barinagarrementeria F: Predictive factors for intracerebral hemorrhage in patients with cavernous angiomas. Neurol Res 27:314318, 2005

    • Search Google Scholar
    • Export Citation
  • 15

    Dammann P, , Barth M, , Zhu Y, , Maderwald S, , Schlamann M, & Ladd ME, et al.: Susceptibility weighted magnetic resonance imaging of cerebral cavernous malformations: prospects, drawbacks, and first experience at ultra-high field strength (7-Tesla) magnetic resonance imaging. Neurosurg Focus 29:3 E5, 2010

    • Search Google Scholar
    • Export Citation
  • 16

    Del Curling O Jr, , Kelly DL Jr, , Elster AD, & Craven TE: An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702708, 1991

    • Search Google Scholar
    • Export Citation
  • 17

    Detwiler PW, , Porter RW, , Zabramski JM, & Spetzler RF: De novo formation of a central nervous system cavernous malformation: implications for predicting risk of hemorrhage. Case report and review of the literature. J Neurosurg 87:629632, 1997

    • Search Google Scholar
    • Export Citation
  • 18

    Frim DM, & Scott RM: Management of cavernous malformations in the pediatric population. Neurosurg Clin N Am 10:513518, 1999

  • 19

    Gaensler EH, , Dillon WP, , Edwards MS, , Larson DA, , Rosenau W, & Wilson CB: Radiation-induced telangiectasia in the brain simulates cryptic vascular malformations at MR imaging. Radiology 193:629636, 1994

    • Search Google Scholar
    • Export Citation
  • 20

    Gangemi M, , Longatti P, , Maiuri F, , Cinalli G, & Carteri A: Cerebral cavernous angiomas in the first year of life. Neurosurgery 25:465469, 1989

    • Search Google Scholar
    • Export Citation
  • 21

    Giulioni M, , Acciarri N, , Padovani R, , Frank F, , Galassi E, & Gaist G: Surgical management of cavernous angiomas in children. Surg Neurol 42:194199, 1994

    • Search Google Scholar
    • Export Citation
  • 22

    Giulioni M, , Acciarri N, , Padovani R, & Galassi E: Results of surgery in children with cerebral cavernous angiomas causing epilepsy. Br J Neurosurg 9:135141, 1995

    • Search Google Scholar
    • Export Citation
  • 23

    Gross BA, , Lin N, , Du R, & Day AL: The natural history of intracranial cavernous malformations. Neurosurg Focus 30:6 E24, 2011

  • 24

    Hanauer DA: EMERSE: The Electronic Medical Record Search Engine. AMIA Annu Symp Proc 2006:941, 2006

  • 25

    Heckl S, , Aschoff A, & Kunze S: Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer 94:32853291, 2002

    • Search Google Scholar
    • Export Citation
  • 26

    Heffez DS, , Stein BM, & Sisti MB: Cavernous malformations. J Neurosurg 84:894895, 1996. (Letter)

  • 27

    Herter T, , Brandt M, & Szüwart U: Cavernous hemangiomas in children. Childs Nerv Syst 4:123127, 1988

  • 28

    Katzman GL, , Dagher AP, & Patronas NJ: Incidental findings on brain magnetic resonance imaging from 1000 asymptomatic volunteers. JAMA 282:3639, 1999

    • Search Google Scholar
    • Export Citation
  • 29

    Kim DS, , Park YG, , Choi JU, , Chung SS, & Lee KC: An analysis of the natural history of cavernous malformations. Surg Neurol 48:918, 1997

  • 30

    Kivelev J, , Niemelä M, , Kivisaari R, , Dashti R, , Laakso A, & Hernesniemi J: Long-term outcome of patients with multiple cerebral cavernous malformations. Neurosurgery 65:450455, 2009

    • Search Google Scholar
    • Export Citation
  • 31

    Kon T, , Mori H, , Hasegawa K, , Nishiyama K, , Tanaka R, & Takahashi H: Neonatal cavernous angioma located in the basal ganglia with profuse intraoperative bleeding. Childs Nerv Syst 23:449453, 2007

    • Search Google Scholar
    • Export Citation
  • 32

    Kondziolka D, , Lunsford LD, , Flickinger JC, & Kestle JR: Reduction of hemorrhage risk after stereotactic radiosurgery for cavernous malformations. J Neurosurg 83:825831, 1995

    • Search Google Scholar
    • Export Citation
  • 33

    Kondziolka D, , Lunsford LD, & Kestle JR: The natural history of cerebral cavernous malformations. J Neurosurg 83:820824, 1995

  • 34

    Kupersmith MJ, , Kalish H, , Epstein F, , Yu G, , Berenstein A, & Woo H, et al.: Natural history of brainstem cavernous malformations. Neurosurgery 48:4754, 2001

    • Search Google Scholar
    • Export Citation
  • 35

    Labauge P, , Brunereau L, , Laberge S, & Houtteville JP: Prospective follow-up of 33 asymptomatic patients with familial cerebral cavernous malformations. Neurology 57:18251828, 2001

    • Search Google Scholar
    • Export Citation
  • 36

    Labauge P, , Brunereau L, , Lévy C, , Laberge S, & Houtteville JP: The natural history of familial cerebral cavernomas: a retrospective MRI study of 40 patients. Neuroradiology 42:327332, 2000

    • Search Google Scholar
    • Export Citation
  • 37

    Larson JJ, , Ball WS, , Bove KE, , Crone KR, & Tew JM Jr: Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J Neurosurg 88:5156, 1998

    • Search Google Scholar
    • Export Citation
  • 38

    Lee JW, , Kim DS, , Shim KW, , Chang JH, , Huh SK, & Park YG, et al.: Management of intracranial cavernous malformation in pediatric patients. Childs Nerv Syst 24:321327, 2008

    • Search Google Scholar
    • Export Citation
  • 39

    Maraire JN, & Awad IA: Intracranial cavernous malformations: lesion behavior and management strategies. Neurosurgery 37:591605, 1995

  • 40

    Mathiesen T, , Edner G, & Kihlström L: Deep and brainstem cavernomas: a consecutive 8-year series. J Neurosurg 99:3137, 2003

  • 41

    Mazza C, , Scienza R, , Beltramello A, & Da Pian R: Cerebral cavernous malformations (cavernomas) in the pediatric age-group. Childs Nerv Syst 7:139146, 1991

    • Search Google Scholar
    • Export Citation
  • 42

    Moriarity JL, , Clatterbuck RE, & Rigamonti D: The natural history of cavernous malformations. Neurosurg Clin N Am 10:411417, 1999

  • 43

    Moriarity JL, , Wetzel M, , Clatterbuck RE, , Javedan S, , Sheppard JM, & Hoenig-Rigamonti K, et al.: The natural history of cavernous malformations: a prospective study of 68 patients. Neurosurgery 44:11661173, 1999

    • Search Google Scholar
    • Export Citation
  • 44

    Morris Z, , Whiteley WN, , Longstreth WT Jr, , Weber F, , Lee YC, & Tsushima Y, et al.: Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 339:b3016, 2009

    • Search Google Scholar
    • Export Citation
  • 45

    Mottolese C, , Hermier M, , Stan H, , Jouvet A, , Saint-Pierre G, & Froment JC, et al.: Central nervous system cavernomas in the pediatric age group. Neurosurg Rev 24:5573, 2001

    • Search Google Scholar
    • Export Citation
  • 46

    Nimjee SM, , Powers CJ, & Bulsara KR: Review of the literature on de novo formation of cavernous malformations of the central nervous system after radiation therapy. Neurosurg Focus 21:1 e4, 2006

    • Search Google Scholar
    • Export Citation
  • 47

    Ondra SL, , Troupp H, , George ED, & Schwab K: The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 73:387391, 1990

    • Search Google Scholar
    • Export Citation
  • 48

    Otten P, , Pizzolato GP, , Rilliet B, & Berney J: [131 cases of cavernous angioma (cavernomas) of the CNS, discovered by retrospective analysis of 24,535 autopsies.]. Neurochirurgie 35:8283, 1989. (Fr)

    • Search Google Scholar
    • Export Citation
  • 49

    Pollock BE, , Garces YI, , Stafford SL, , Foote RL, , Schomberg PJ, & Link MJ: Stereotactic radiosurgery for cavernous malformations. J Neurosurg 93:987991, 2000

    • Search Google Scholar
    • Export Citation
  • 50

    Porter PJ, , Willinsky RA, , Harper W, & Wallace MC: Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg 87:190197, 1997

    • Search Google Scholar
    • Export Citation
  • 51

    Porter RW, , Detwiler PW, , Spetzler RF, , Lawton MT, , Baskin JJ, & Derksen PT, et al.: Cavernous malformations of the brainstem: experience with 100 patients. J Neurosurg 90:5058, 1999

    • Search Google Scholar
    • Export Citation
  • 52

    Pozzati E, , Acciarri N, , Tognetti F, , Marliani F, & Giangaspero F: Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery 38:662670, 1996

    • Search Google Scholar
    • Export Citation
  • 53

    Reid PJ, , Campbell SS, , Vates GE, & Allende R: Extreme de novo appearance of cerebral cavernous malformations: case report. Neurosurgery 62:E969E970, 2008

    • Search Google Scholar
    • Export Citation
  • 54

    Rigamonti D, & Spetzler RF: The association of venous and cavernous malformations. Report of four cases and discussion of the pathophysiological, diagnostic, and therapeutic implications. Acta Neurochir (Wien) 92:100105, 1988

    • Search Google Scholar
    • Export Citation
  • 55

    Robinson JR, , Awad IA, & Little JR: Natural history of the cavernous angioma. J Neurosurg 75:709714, 1991

  • 56

    Sarwar M, & McCormick WF: Intracerebral venous angioma. Case report and review. Arch Neurol 35:323325, 1978

  • 57

    Scott RM, , Barnes P, , Kupsky W, & Adelman LS: Cavernous angiomas of the central nervous system in children. J Neurosurg 76:3846, 1992

  • 58

    Sheehan J, & Schlesinger D: Editorial. Radiosurgery and cavernous malformations. J Neurosurg 113:689690, 2010

  • 59

    Vernooij MW, , Ikram MA, , Tanghe HL, , Vincent AJ, , Hofman A, & Krestin GP, et al.: Incidental findings on brain MRI in the general population. N Engl J Med 357:18211828, 2007

    • Search Google Scholar
    • Export Citation
  • 60

    Washington CW, , McCoy KE, & Zipfel GJ: Update on the natural history of cavernous malformations and factors predicting aggressive clinical presentation. Neurosurg Focus 29:3 E7, 2010

    • Search Google Scholar
    • Export Citation
  • 61

    Wurm G, , Schnizer M, & Fellner FA: Cerebral cavernous malformations associated with venous anomalies: surgical considerations. Neurosurgery 57:1 Suppl 4258, 2005

    • Search Google Scholar
    • Export Citation
  • 62

    Xia C, , Zhang R, , Mao Y, & Zhou L: Pediatric cavernous malformation in the central nervous system: report of 66 cases. Pediatr Neurosurg 45:105113, 2009

    • Search Google Scholar
    • Export Citation
  • 63

    Yue NC, , Longstreth WT Jr, , Elster AD, , Jungreis CA, , O'Leary DH, & Poirier VC: Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. Radiology 202:4146, 1997

    • Search Google Scholar
    • Export Citation
  • 64

    Zabramski JM, , Wascher TM, , Spetzler RF, , Johnson B, , Golfinos J, & Drayer BP, et al.: The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 80:422432, 1994

    • Search Google Scholar
    • Export Citation
  • 65

    Zacharia BE, , Hickman ZL, , Grobelny BT, , DeRosa P, , Kotchetkov I, & Ducruet AF, et al.: Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurg Clin N Am 21:221233, 2010

    • Search Google Scholar
    • Export Citation
  • 66

    Zimmerman RS, , Spetzler RF, , Lee KS, , Zabramski JM, & Hargraves RW: Cavernous malformations of the brain stem. J Neurosurg 75:3239, 1991

Metrics

All Time Past Year Past 30 Days
Abstract Views 1186 316 25
Full Text Views 279 74 4
PDF Downloads 278 83 3
EPUB Downloads 0 0 0