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  • Natural History of Cavernous Malformation: Systematic Review and Meta-analysis of 25 Studies, Identifying Source of Heterogeneity

    Final Number:
    532

    Authors:
    Shervin Taslimi; amirhossein modabbernia; Sepideh Amin-Hanjani MD, FAANS, FACS, FAHA; Frederick George Barker MD; R. Loch Macdonald MD, PhD

    Study Design:
    Other

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting

    Introduction: Cavernous malformations (CM) have a varied natural history. We pooled the result of studies on natural history of cavernous malformations (CM) to calculate point estimates and investigate main sources of heterogeneity.

    Methods: We searched MEDLINE, EMBASE, and ISI Web of Science for relevant studies published before May 2015. We used fixed and random effects models and meta-regression to pool the data.

    Results: 25 studies were entered into the meta-analysis (90-1295 patients depending on the analysis). Bleeding was defined as symptomatic hemorrhage plus radiologic evidence of hemorrhage. Sources of heterogeneity identified as mixture of hemorrhage and re-hemorrhage, mixture of re-hemorrhage before and after two years of first bleeding, brainstem versus other locations, and calculation method (type of calculating PY or LY of follow up). The re-hemorrhage rate was higher than the hemorrhage rate (incidence rate ratio 16.5, P<0.001, 95%CI [9.7-28.0]). Re-hemorrhage within two years of the first hemorrhage was higher than after that (incidence rate ratio: 1.8, P=0.042, 95%CI [1.5-2.0]). In two meta-regression models (for hemorrhage and re-hemorrhage), percentage of brainstem lesions in each study decreased the heterogeneity considerably. Based on the model, rough estimate of the annual incidence rate of hemorrhage was 0.3% (95% CI 0.1%-0.5%) and 2.8% (2.5%-3.3%) per person year (PY) in non-brainstem and brainstem lesions. Rough estimate of annual re-hemorrhage rate per PY was 6.3% (3%-13.2%) and 32.3% (19.8%-52.7%) in non-brainstem and brainstem lesions. Median time to rehemorrhage was 10.5 months. Post hemorrhage full recovery was 38.8%/PY (28.7%-48.8%). Post hemorrhage full recovery or minimal disability was 79.5%/PY (74.3%-84.8%). Mortality after bleeding was 2.2%.

    Conclusions: Bleeding in cavernomas confers low risk of death and morbidity. Location of the lesions is an important risk factor for symptomatic hemorrhage (brainstem location). Prior hemorrhage increases the risk of re-hemorrhage. Re-hemorrhage is more common during the first two years after the first bleeding.

    Patient Care: Results of this study helps neurosurgeons to identify different subgroups of patients with cavernous malformation and combined with the risk of surgery helps them to decide about the type of treatment they want to offer to the patients with cavernous malformation. Patients can also be involved more in their care by knowing the natural history of the disease. This study also reduces the confusion around different risk factors for cavernoma bleeding and helps neurosurgeons to base their decision on true risk factors of bleeding and ignore some identified risk factors in published studies that need further assessment.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe sources of heterogeneity in studies reporting natural history of cavernous malformation, 2) Describe different subgroups of patients with cavernous malformation at the risk of hemorrhage and re-hemorrhage 3) Identify the risk factors for hemorrhage and re-hemorrhage, 4) differentiate between scietifically proven risk factors of hemorrhage and those which need to be further assessed,5) Discuss, in small groups the appropriate methodology of conducting a natural history study in patients with cavernous malformation and using appropriate outcome measures 6) describe potentially suitable patients who might benefit from the surgery, knowing the risk of the surgery.

    References: No references

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