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Risk of Prospective Hemorrhage is Found to be Low in Patients With Incidentally Discovered Intracerebral Cavernous Malformations

Rukovets, Olga

doi: 10.1097/01.NT.0000429370.39388.d0
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At the AAN annual meeting, investigators presented new research on risk of prospective hemorrhage in patients with incidentally discovered ICM diagnosed between 1989 and 1999.

As many as half of all intracerebral cavernous malformations (ICMs) — collections of capillaries in the brain that are enlarged and irregular in structure — are asymptomatic and discovered incidentally. Although some data exist on the natural history of these lesions, they are normally found within studies that don't differentiate between symptomatic presentation (i.e., seizure or hemorrhage) and incidental discovery with asymptomatic presentation, according to Samuel Arthur Moore, MD, of the Mayo Clinic in Rochester, MN, and colleagues, who presented new research on ICMs at last month's annual meeting of the American Academy of Neurology.

Previous studies have also had a limited follow up duration — typically two to 10 years, Dr. Moore and colleagues wrote. In response to these limitations, the Mayo Clinic researchers set out to study incidentally discovered ICMs and define their natural history over a long period of follow-up. They concluded that “the risk of prospective hemorrhage in patients presenting asymptomatically with ICM is very low.”

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Dr. Moore and colleagues analyzed data from 110 patients with incidentally discovered ICM diagnosed between 1989 and 1999 who were identified in a previously published cohort [see for more information on those findings].

Using medical chart review and a mail survey, the researchers were able to obtain updated clinical and radiographic data pertaining to symptomatic intracerebral hemorrhage related to the ICM. Prospective hemorrhage rate was calculated by dividing the number of prospective hemorrhages by the number of patient-years of follow-up.

Nearly half the patients were male (46.4 percent male; mean age of diagnosis 52.5 years), and 1,324 patient-years of follow up were obtained. Twenty-four deaths occurred since previous follow-up, and cause of death was determined in 17 cases. Three patients had a prospective hemorrhage, so bleed rate was determined to be 0.23 per 100 person-years of follow-up. Five of the patients had developed seizures since previous follow-up.

Overall, the researchers concluded that there is a very low risk of prospective hemorrhage in those patients who have incidentally discovered ICMs. “This information can be useful in management decisions,” they wrote.

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Issam Awad, MD, John Harper Seeley professor of surgery and director of neurovascular surgery at the University of Chicago School of Medicine, said that a low prospective risk of hemorrhage with asymptomatic ICM “has been reported before with similar range of estimated risk.”

However, he added, other studies have differentiated risk of hemorrhage depending on the location of the lesion, indicating “a significantly higher risk of hemorrhage of lesions in deep and infratentorial location [below the tentorium cerebelli]. It is unclear how many deep and infratentorial lesions were included in this cohort.

“Also, this study necessarily excluded cases that underwent elective excision of the lesion for whatever reason (larger lesion, younger patient, solitary versus familial cases with varying disease severity in different genotypes, etc.),” he added, and it would be premature to generalize this same risk to all asymptomatic ICMs.

Gregory P. Lekovic, MD, PhD, neurosurgeon in private practice with the House Clinic Neurosurgical Associates, told Neurology Today in a telephone interview that the study was important because, “with greater prevalence and routine use of MRI imaging in particular, more and more cavernous malformations are being detected on an incidental basis. But we don't know necessarily what the natural history — or the likely outcome after the diagnosis — is when we discover an ICM incidentally as opposed to one that presents with hemorrhage or seizure or in a more usual way.”

The strength of this study, according to Dr. Lekovic, was the very long-term follow up of more than a thousand patient-years. “This is a nice contribution,” he said, to currently available literature on ICMs.

Dr. Lekovic added that the limitation here is that the authors “did not or were unable to differentiate the location of cavernous malformations and the impact that location would have on hemorrhage rate.

“That's been a key issue in the discussion or management of the disease. Specifically, a cavernous malformation that's located in the supratentorial compartment of the brain cortex that's discovered incidentally or presents with seizure will have a very low hemorrhage risk and we've known that, whereas cavernous malformations that present in the brain stem or in other eloquent areas like the basal ganglia or the thalamus appear to have a much higher symptomatic bleed rate,” Dr. Lekovic told Neurology Today. Therefore, he concurred that it would be misleading to use these findings for guidance in patients with deep-seated ICMs.

The authors also did not appear to consider prospective risk of seizure, Dr. Awad pointed out. “This has been estimated to exceed the annual risk of hemorrhage in cortical lesions, and it is unclear how seizures may have affected the selection of cases for follow-up versus surgery.”

The bleed rate in this study — 0.23 per hundred-person-years of follow-up — was very low, noted Dr. Lekovic, and is “lower than the conventional wisdom, which would say that for a single cavernous malformation, the rate of bleeding would be near 0.1 percent to 0.8 or 1 percent per annum.” But even a 0.23-percent-per-year hemorrhage risk, Dr. Awad added, is not trivial in patients with several decades of life expectancy.

Any data that we can get regarding the incidence and history of ICMs is welcome, said Dr. Lekovic, since the incidence of ICMs is “probably much larger than commonly appreciated by primary care physicians and even amongst practicing neurologists and neurosurgeons. Awareness of the disease needs to be raised.”

Importantly, we need to be able to determine the rate of hemorrhage in eloquent lesions in order to better guide therapy, he said.

After conducting long-term follow-up of patients with incidentally discovered intracerebral cavernous malformations (ICMs), investigators reported that the risk of prospective hemorrhage in these patients was very low. Here, Neurology Today Editor in Chief Steven P. Ringel, MD, and Neurology Today Associate Editor Robert Holloway, MD, offer in-depth insights into what these findings may mean for clinicians:

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•. Flemming KD, Link MJ, Brown RD, et al.Prospective hemorrhage risk of intracerebral cavernous malformations. Neurology 2012; 78(9): 632–636.
•. Neurology Today's archive on cavernous malformation:
•. Study abstract from AAN annual meeting:
©2013 American Academy of Neurology