The Natural History of Cavernous Malformations: A Prospective Study of 68 Patients

Moriarity, John L.; Wetzel, Matthew; Clatterbuck, Richard E.; Javedan, Sam; Sheppard, Jeannie-Marie E.; Hoenig-Rigamonti, Karen; Crone, Nathan E.; Breiter, Steven N.; Lee, Roland R.; Rigamonti, Daniele

doi:10.1227/00006123-199906000-00003

Cited by 119 publications

(243 citation statements)

References 20 publications

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…Robinson et al 26 reported an annual hemorrhage rate of 0.7% per lesion-year. The studies of Kondziolka et al, 15 Moriarity et al, 20 and Porter et al 23 reported annual hemorrhage rates ranging from 1.6% to 3.1% per patient-year. Across these 3 studies including a total of 363 patients followed up for 1121.5 patient-years, the overall hemorrhage rate was 2.4% per patient-year.…”

Section: Hemorrhagementioning

confidence: 98%

“…Across these 3 studies including a total of 363 patients followed up for 1121.5 patient-years, the overall hemorrhage rate was 2.4% per patient-year. 15,20,23 Rates are calculated per patient-year by taking the quotient of total number of hemorrhages experienced by an individual patient and the number of years the patient is followed up. Thus, patients with multiple lesions may have higher hemorrhage rates as calculated per patient-year as opposed to per lesion-year; the latter is the quotient of number of hemorrhages per lesion and years followed.…”

Section: Hemorrhagementioning

confidence: 99%

“…2,7,14,20,23,26,31 Across 7 general distribution studies with 656 patients, 125 patients (19%) harbored multiple intracranial CMs. 7,8,14,15,20,23,26 Developmental venous anomalies were seen in 54 (9%) of 593 patients in 6 studies reporting associated vascular malformations. 7,15,20,23,26,31 Table 2 summarizes overall epidemiological, clinical presentation, and hemorrhage rate data.…”

mentioning

confidence: 99%

“…7,8,14,15,20,23,26 Developmental venous anomalies were seen in 54 (9%) of 593 patients in 6 studies reporting associated vascular malformations. 7,15,20,23,26,31 Table 2 summarizes overall epidemiological, clinical presentation, and hemorrhage rate data.…”

mentioning

confidence: 99%

See 3 more Smart Citations

The natural history of intracranial cavernous malformations

Gross

Lin

et al. 2011

FOC

276

243

View full text Add to dashboard Cite

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.

show abstract

Section: Hemorrhagementioning

confidence: 98%

Section: Hemorrhagementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The natural history of intracranial cavernous malformations

Gross

Lin

et al. 2011

FOC

276

243

View full text Add to dashboard Cite

show abstract

“…Collectively, our data suggest that the origin of CCM lesions is caused by perturbed Notch signaling-induced excessive capillary sprouting, which can be therapeutically targeted. C erebral cavernous malformations (CCM) [OMIM: 116860] are frequent vascular abnormalities, predominately localized in the brain, affecting up to 0.5% of the human population (1). CCM lesions are characterized by grossly enlarged vascular channels, often lacking support of mural cells.…”

mentioning

confidence: 99%

Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling

Wüstehube

Bartol

Liebler

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

177

144

View full text Add to dashboard Cite

Cerebral cavernous malformations (CCM) are frequent vascular abnormalities caused by mutations in one of the CCM genes. CCM1 (also known as KRIT1) stabilizes endothelial junctions and is essential for vascular morphogenesis in mouse embryos. However, cellular functions of CCM1 during the early steps of the CCM pathogenesis remain unknown. We show here that CCM1 represents an antiangiogenic protein to keep the human endothelium quiescent. CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells. CCM1 strongly induces DLL4-NOTCH signaling, which promotes AKT phosphorylation but reduces phosphorylation of the mitogen-activated protein kinase ERK. Consistently, blocking of NOTCH activity alleviates CCM1 effects. ERK phosphorylation is increased in human CCM lesions. Transplantation of CCM1-silenced human endothelial cells into SCID mice recapitulates hallmarks of the CCM pathology and serves as a unique CCM model system. In this setting, the multikinase inhibitor Sorafenib can ameliorate loss of CCM1-induced excessive microvascular growth, reducing the microvessel density to levels of normal wild-type endothelial cells. Collectively, our data suggest that the origin of CCM lesions is caused by perturbed Notch signaling-induced excessive capillary sprouting, which can be therapeutically targeted.endothelial cells | vascular malformations | CCM | KRIT1

show abstract

Value of Gradient-Echo Magnetic Resonance Imaging in the Diagnosis of Familial Cerebral Cavernous Malformation

Lehnhardt¹,

Smekal²,

Rückriem³

et al. 2005

Arch Neurol

View full text Add to dashboard Cite

Background: Cerebral cavernous malformations (CCMs) are congenital vascular anomalies that can cause seizures, intracranial hemorrhages, focal neurological deficits, and migrainelike headaches. Magnetic resonance (MR) imaging has substantially facilitated diagnosis of CCM. It is now widely accepted that familial clustering with an autosomal dominant inheritance pattern should be suspected in cases of multiple lesions. Objective: To determine by MR imaging the penetrance of cavernous malformations in a 3-generation family that included 5 members with typical clinical signs and diagnostic findings. Methods: All family members underwent routine MR T1-weighted and T2-weighted spin-echo sequences in addition to MR T2-weighted gradient-echo sequences. Results: Four family members had been symptomatic with either brainstem bleeding, headaches, or focal neurological signs. The gradient-echo sequences yielded a dramatically higher sensitivity with regard to lesion number and distribution. As in previous reports of familial CCM, an increase in lesion number with increasing age, changes in lesion characteristics, de novo occurrence in serial MR imaging over time, and the phenomenon of anticipation could be confirmed in this family. Conclusion: Magnetic resonance gradient-echo sequences should be considered the method of choice for diagnosis of familial CCM.

show abstract

The Natural History of Cavernous Malformations: A Prospective Study of 68 Patients

Cited by 119 publications

References 20 publications

The natural history of intracranial cavernous malformations

The natural history of intracranial cavernous malformations

Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling

Value of Gradient-Echo Magnetic Resonance Imaging in the Diagnosis of Familial Cerebral Cavernous Malformation

Contact Info

Product

Resources

About