The natural history of intracranial cavernous malformations
Neurosurg Focus 30 (6):E24, 2011 1 C avernous malformations are clusters of dilated sinusoidal channels lined by a single layer of endothelium. 3, 8, 19, 20, 26 In contradistinction to arteriovenous malformations, these lesions do not have smooth muscle or elastin in their lining, and they are angiographically occult. Their prevalence across several reports ranges from 0.4% to 0.6% of the population. 8, 14, 22, 26, 27 Since 1991, multiple natural history reports have surfaced in the literature,
... in the literature, with significant dissension in regard to lesion epidemiology and particularly hemorrhage risk. Herein, we review 11 studies describing the epidemiology, clinical presentation, and natural history of these lesions in an attempt to elicit more cogent data so as to clarify hemorrhage rates and risk factors for bleeding. Methods A PubMed search using the terms "cavernoma," "cavernous malformation," "cavernous hemangioma," "natural history," "bleed," and "hemorrhage" was performed. To minimize bias and to more naturally reflect the clinical course of these lesions, surgical series were excluded, leaving a total of 11 retrospective and prospec-tive natural history studies in the English-language literature for analysis. Accounting for de novo CM development after birth, 4 retrospective studies were excluded from our analysis of CM hemorrhage rates. Results Epidemiology and Clinical Presentation Epidemiological data and information on patient presentation were extracted from 10 natural history studies with a total of 837 patients (Table 1 ). The male-tofemale ratio was 1:1 (422 males and 415 females). The mean age at presentation was 30.6 years. Across 9 studies with 775 patients providing data on clinical presentation, 37% presented with seizures, 36% with hemorrhage, 23% with headaches, and 22% with focal neurological deficits (some patients had more than one). 2, 7, 8, 15, 17, 20, 23, 26, 31 Ten percent of patients were asymptomatic. Across 9 series providing applicable data on cerebral CM location in 1055 patients, 803 (76%) were supratentorial, 243 (23%) were infratentorial, and 9 (1%) were both. 2, 7, 8, 14, 17, 20, 23, 26, 31 Across 7 studies with 747 cerebral CMs providing further detailed information on lesion location, 491 lesions (66%) were located in the cerebral hemisphere (lobar), 131 (18%) in the brainstem, 61 (8.2%) Literature reports on the natural history of cerebral cavernous malformations (CMs) are numerous, with considerable variability in lesion epidemiology, hemorrhage rates, and risk factors for hemorrhage. In this review, the authors performed a meta-analysis of 11 natural history studies. The overall male-to-female ratio was 1:1, and the mean age at presentation was 30.6 years. Overall, 37% of patients presented with seizures, 36% with hemorrhage, 23% with headaches, 22% with focal neurological deficits, and 10% were asymptomatic. Some patients had more than one symptom. Seizure presentation was most prevalent among supratentorial CMs, while focal neurological deficits were common in patients with infratentorial CMs. By location, CMs were in the cerebral hemispheres (66%), brainstem (18%), basal ganglia or thalamus (8%), cerebellum (6%), and other (2.5% [combined supra-and infratentorial, callosal or insular]). Overall, 19% of patients harbored multiple intracranial CMs, and 9% had radiographically apparent associated developmental venous anomalies. An overall annual hemorrhage rate of 2.4% per patient-year (range 1.6%-3.1%) was identified across 3 studies. Prior hemorrhage and female sex were risk factors for bleeding, while CM size and multiplicity did not affect hemorrhage rates. Although not impacting the hemorrhage rate itself, deep location was a risk factor for increased clinical aggressiveness. Key Words • cavernous malformation • cavernoma • hemorrhage • natural history 1 Abbreviations used in this paper: CM = cavernous malformation; DVA = developmental venous anomaly.