Natural history and treatment options of radiation-induced brain cavernomas: a systematic review

AbstractRadiation-induced cavernous malformations (RICMs) are delayed complications of brain irradiation during childhood. Its natural history is largely unknown and its incidence may be underestimated as RCIMS tend to develop several years following radiation. No clear consensus exists regarding the long-term follow-up or treatment. A systematic review of Embase, Cochrane Library, PubMed, Google Scholar, and Web of Science databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed. Based on our inclusion/exclusion criteria, 12 articles were included, totaling 113 children with RICMs, 86 were treated conservatively, and 27 with microsurgery. We were unable to precisely define the incidence and natural history from this data. The mean age at radiation treatment was 7.3 years, with a slight male predominance (54%) and an average dose of 50.0 Gy. The mean time to detection of RICM was 9.2 years after radiation. RICM often developed at distance from the primary lesion, more specifically frontal (35%) and temporal lobe (34%). On average, 2.6 RICMs were discovered per child. Sixty-seven percent were asymptomatic. Twenty-one percent presented signs of hemorrhage. Clinical outcome was favorable in all children except in 2. Follow-up data were lacking in most of the studies. RICM is most often asymptomatic but probably an underestimated complication of cerebral irradiation in the pediatric population. Based on the radiological development of RICMs, many authors suggest a follow-up of at least 15 years. Studies suggest observation for asymptomatic lesions, while surgery is reserved for symptomatic growth, hemorrhage, or focal neurological deficits.

Brainstem cavernous malformations: the role of Gamma Knife surgery

10.3171/2012.8.gks121066 ◽

2012 ◽

Vol 117 (Special_Suppl) ◽

pp. 164-169 ◽

Cited By ~ 13

Author(s):

Cheng-Chia Lee ◽

David Hung-Chi Pan ◽

Wen-Yuh Chung ◽

Kang-Du Liu ◽

Huai-Che Yang ◽

...

Keyword(s):

Gamma Knife ◽

Good Alternative ◽

Gamma Knife Surgery ◽

Neurological Deficits ◽

Cavernous Malformations ◽

Perifocal Edema ◽

Consciousness Disturbance ◽

Radiation Induced ◽

Object The authors retrospectively reviewed the efficacy and safety of Gamma Knife surgery (GKS) in patients with brainstem cavernous malformations (CMs). The CMs had bled repeatedly and placed the patients at high risk with respect to surgical intervention. Methods Between 1993 and 2010, 49 patients with symptomatic CMs were treated by GKS. The mean age in these patients was 37.8 years, and the predominant sex was female (59.2%). All 49 patients experienced at least 2 instances of repeated bleeding before GKS; these hemorrhages caused neurological deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, chorea or athetosis, and consciousness disturbance. Results The mean size of the CMs at the time of GKS was 3.2 cm3 (range 0.1–14.6 cm3). The mean radiation dose directed to the lesion was 11 Gy with an isodose level at 60.0%. The mean clinical and imaging follow-up time was 40.6 months (range 1.0–150.7 months). Forty-five patients participated in regularly scheduled follow-up. Twenty-nine patients (59.2%) were followed up for > 2 years, and 16 (32.7%) were followed up for < 2 years. The pre-GKS annual hemorrhage rate was 31.3% (69 symptomatic hemorrhages during a total of 220.3 patient-years). After GKS, 3 episodes of symptomatic hemorrhage were observed within the first 2 years of follow-up (4.29% annual hemorrhage rate), and 3 episodes of symptomatic hemorrhage were observed after the first 2 years of follow-up (3.64% annual hemorrhage rate). In this study of 49 patients, symptomatic radiation-induced complications developed in only 2 patients (4.1%; cyst formation in 1 patient and perifocal edema with neurological deficits in the other patient). There were no deaths in this group. Conclusions Gamma Knife surgery is effective in reducing the rate of recurrent hemorrhage. In the authors' experience, it was possible to control bleeding using a low-dose treatment. In addition, there were few symptomatic radiation-induced complications. As a result, the authors believe that GKS is a good alternative treatment for brainstem CMs.

Coexistence of intracranial and spinal cavernous malformations: a study of prevalence and natural history

10.3171/jns.2006.104.3.376 ◽

2006 ◽

Vol 104 (3) ◽

pp. 376-381 ◽

Cited By ~ 47

Author(s):

Aaron A. Cohen-Gadol ◽

Jeffrey T. Jacob ◽

Diane A. Edwards ◽

William E. Krauss

Keyword(s):

Family History ◽

Natural History ◽

Mr Imaging ◽

Neurological Deficits ◽

Cavernous Malformations ◽

Recurrent Hemorrhage ◽

Long Term Follow Up ◽

History Of ◽

Clinically Significant

Object The purpose of this study was to examine the prevalence of intracranial cavernous malformations (CMs) in a large series of predominantly Caucasian patients with spinal cord CMs. The authors also studied the natural history of spinal CMs in patients who were treated nonoperatively. Methods The medical records of 67 consecutive patients (32 female and 35 male patients) in whom a spinal CM was diagnosed between 1994 and 2002 were reviewed. The patients’ mean age at presentation was 50 years (range 13–82 years). Twenty-five patients underwent resection of the lesion. Forty-two patients in whom the spinal CM was diagnosed using magnetic resonance (MR) imaging were followed expectantly. Thirty-three (49%) of 67 patients underwent both spinal and intracranial MR imaging. All available imaging studies were reviewed to determine the coexistence of an intracranial CM. Fourteen (42%) of the 33 patients with spinal CMs who underwent intracranial MR imaging harbored at least one cerebral CM in addition to the spinal lesion. Six (43%) of these 14 patients did not have a known family history of CM. Data obtained during the long-term follow-up period (mean 9.7 years, total of 319 patient-years) were available for 33 of the 42 patients with a spinal CM who did not undergo surgery. Five symptomatic lesional hemorrhages (neurological events), four of which were documented on neuroimaging studies, occurred during the follow-up period, for an overall event rate of 1.6% per patient per year. No patient experienced clinically significant neurological deficits due to recurrent hemorrhage. Conclusions As many as 40% of patients with a spinal CM may harbor a similar intracranial lesion, and approximately 40% of patients with coexisting spinal and intracranial CMs may have the nonfamilial (sporadic) form of the disease. Patients with symptomatic spinal CMs who are treated nonoperatively may have a small risk of clinically significant recurrent hemorrhage. The findings will aid in evaluation of surveillance images and in counseling of patients with spinal CMs, irrespective of family history.

Articular Cartilage Repair of the Pediatric and Adolescent Knee with Regard to Minimal Clinically Important Difference: A Systematic Review

Cartilage ◽

10.1177/1947603518783503 ◽

2018 ◽

Vol 11 (1) ◽

pp. 9-18 ◽

Cited By ~ 5

Author(s):

Rosa S. Valtanen ◽

Armin Arshi ◽

Benjamin V. Kelley ◽

Peter D. Fabricant ◽

Kristofer J. Jones

Keyword(s):

Systematic Review ◽

Articular Cartilage ◽

Clinical Outcomes ◽

Cartilage Repair ◽

Minimal Clinically Important Difference ◽

Cochrane Library ◽

Clinically Important Difference ◽

Outcome Score ◽

Objective To perform a systematic review of clinical outcomes following microfracture (MFX), autologous chondrocyte implantation (ACI), osteochondral allograft transplantation (OCA), and osteochondral autograft transplantation system (OATS) to treat articular cartilage lesions in pediatric and adolescent patients. We sought to compare postoperative improvements for each cartilage repair method to minimal clinically important difference (MCID) thresholds. Design MEDLINE, Web of Science, Scopus, and Cochrane Library databases were searched for studies reporting MCID-validated outcome scores in a minimum of 5 patients ≤19 years treated for symptomatic knee chondral lesions with minimum 1-year follow-up. One-sample t tests were used to compare mean outcome score improvements to established MCID thresholds. Results Twelve studies reporting clinical outcomes on a total of 330 patients following cartilage repair were identified. The mean age of patients ranged from 13.7 to 16.7 years and the mean follow-up was 2.2 to 9.6 years. Six studies reported on ACI, 4 studies reported on MFX, 2 studies reported on OATS, and 1 study reported on OCA. ACI ( P < 0.001, P = 0.008) and OCA ( P < 0.001) showed significant improvement for International Knee Documentation Committee (IKDC) scores with regard to MCID while MFX ( P = 0.66) and OATS ( P = 0.11) did not. ACI ( P < 0.001) and OATS ( P = 0.010) both showed significant improvement above MCID thresholds for Lysholm scores. MFX ( P = 0.002) showed visual analog scale (VAS) pain score improvement above MCID threshold while ACI ( P = 0.037, P = 0.070) was equivocal. Conclusions Outcomes data on cartilage repair in the pediatric and adolescent knee are limited. This review demonstrates that all available procedures provide postoperative improvement above published MCID thresholds for at least one reported clinical pain or functional outcome score.

Acute Versus Delayed Surgical Intervention in Multiligament Knee Injuries: A Systematic Review

Orthopaedic Journal of Sports Medicine ◽

10.1177/23259671211027855 ◽

2021 ◽

Vol 9 (10) ◽

pp. 232596712110278

Author(s):

Ryan S. Marder ◽

Husain Poonawala ◽

Jorge I. Pincay ◽

Frank Nguyen ◽

Patrick F. Cleary ◽

...

Keyword(s):

Systematic Review ◽

Functional Outcomes ◽

Surgical Intervention ◽

Intervention Group ◽

Knee Injuries ◽

Cochrane Library ◽

The Mean ◽

Multiligament Knee Injuries ◽

Level 2

Background: The optimal timing of surgical intervention for multiligament knee injuries remains controversial. Purpose: To review the clinical and functional outcomes after acute and delayed surgical intervention for multiligament knee injuries. Study Design: Systematic review; Level of evidence, 4. Methods: We performed a search of the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to September 2020. Eligible studies reported on knee dislocations, multiligament knee injuries, or bicruciate ligament injuries in adult patients (age, ≥18 years). In addition to comparing outcomes between acute and delayed surgical intervention groups, we conducted 3 subgroup analyses for outcomes within isolated knee injuries, knee injuries with concomitant polytrauma/fractures, and high-level (level 2) studies. Results: Included in the analysis were 31 studies, designated as evidence level 2 (n = 3), level 3 (n = 8), and level 4 (n = 20). These studies reported on 2594 multiligament knee injuries sustained by 2585 patients (mean age, 25.1-65.3 years; mean follow-up, 12-157.2 months). At the latest follow-up timepoint, the mean Lysholm (n = 375), International Knee Documentation Committee (IKDC) (n = 286), and Tegner (n = 129) scores for the acute surgical intervention group were 73.60, 67.61, and 5.06, respectively. For the delayed surgical intervention group, the mean Lysholm (n = 196), IKDC (n = 172), and Tegner (n = 74) scores were 85.23, 72.32, and 4.85, respectively. The mean Lysholm (n = 323), IKDC (n = 236), and Tegner (n = 143) scores for our isolated subgroup were 83.7, 74.8, and 5.0, respectively. By comparison, the mean Lysholm (n = 270), IKDC (n = 236), and Tegner (n = 206) scores for the polytrauma/fractures subgroup were 83.3, 64.5, and 5.0, respectively. Conclusion: The results of our systematic review did not elucidate whether acute or delayed surgical intervention produced superior clinical and functional outcomes. Although previous evidence has supported acute surgical intervention, future prospective randomized controlled trials and matched cohort studies must be completed to confirm these findings.

Intracranial cavernous malformation in children: a single-centered experience with 30 consecutive cases

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130006 ◽

2013 ◽

Vol 71 (4) ◽

pp. 220-228 ◽

Cited By ~ 14

Author(s):

Marcelo Campos Moraes Amato ◽

João Flávio Gurjão Madureira ◽

Ricardo Santos de Oliveira

Keyword(s):

Clinical Presentation ◽

Cavernous Malformation ◽

Neurological Deficits ◽

Treatment Modalities ◽

Study Group ◽

Functional Evaluation ◽

Cavernous Malformations ◽

Asymptomatic Patients ◽

Objectives: To determine the clinical presentation and treatment outcome of pediatric intracranial cavernous malformation (CM) in a single-centered institution. Methods: Clinical data review of 30 patients under 18 years-old who had undergone surgery for cavernous malformation from January 1993 to December 2011. Results: The Study Group included 18 males and 12 females (mean age: 8.7 years-old). Symptoms at presentation were seizures (16/30, 53.3%), headache (15/30, 50.0%), and focal neurological deficits (11/30, 36.6%). Multiple cavernous malformations were found in 5/30 (16.6%). According to location, patients were classified in groups: (G1) brain-steam in 5/30 (16.6%), (G2) cerebellum in 2/30 (6.6%), (G3) supratentorial associated with seizures in 16/30 (53.3%), and (G4) supratentorial without seizures in 7/30 (23.3%). Surgical resection was performed in 26 out of 30 (86.6%) patients. The mean follow-up period was 4.1 years. Of 15 children followed-up with preoperative seizures, all were rendered seizure-free after surgery. Conclusions: For symptomatic solitary cavernous malformation, the treatment of choice is complete microsurgical excision preceded by careful anatomical and functional evaluation. For multiple cavernous malformation or asymptomatic patients, the treatment modalities must be cautiously considered.

Contemporary radiosurgery of cerebral cavernous malformations: Part 2. Treatment outcome for hemispheric lesions

10.3171/2018.2.jns171267 ◽

2019 ◽

Vol 130 (6) ◽

pp. 1826-1834 ◽

Cited By ~ 2

Author(s):

Gábor Nagy ◽

Stuart S. Stokes ◽

Loránd G. Erőss ◽

Debapriya Bhattacharyya ◽

John Yianni ◽

...

Keyword(s):

Natural History ◽

Neurological Deficits ◽

Time Interval ◽

Lesion Volume ◽

Cavernous Malformations ◽

Antiepileptic Medication ◽

Deep Lesion ◽

Prescription Isodose

OBJECTIVEThe role of radiosurgery (RS) in treating superficial cavernous malformations (CMs) is insufficiently studied in part because of the disappointing results of early experimental attempts as compared to the mostly safe and effective microsurgery. Nonetheless, because of lesion- or treatment-specific factors, a therapeutic alternative may be required. In this study, the authors aimed to assess the safety of RS in treating superficial CMs and to analyze its long-term effect on hemorrhage rates and epilepsy control.METHODSThe authors conducted a retrospective analysis of 96 patients with 109 CMs located in the cerebral or cerebellar hemispheres and treated with RS between 1995 and 2014. A median of 15 Gy (range 10–25 Gy) was given to the 50% prescription isodose level, lesion volume was 604 mm3 (4–8300 mm3), and the prescription isodose volume was 638.5 mm3 (4–9500 mm3). Outcomes were compared to those of 206 deep-seated lesions reported on in another study. Ninety-five patients had available follow-up, which was a median of 7 years (1–21 years). Median patient age was 42 years (0.5–77) at presentation and 45 (3–80) at treatment. Seventy-one CMs presented with symptomatic hemorrhage, and 52 caused seizures.RESULTSIn the nonhemorrhagic group (37 lesions), one bleed occurred during the follow-up period, for an annual bleed rate of 0.4% per lesion. The lifetime annual bleed rate of CMs having a single hemorrhage prior to treatment was 2.5%. The rebleed rate in the single-bleed group decreased from 1.8% within the first 2 years after RS to 0.7% thereafter. The pretreatment rebleed rate for lesions having multiple bleeds prior to RS was 14.15%, which fell to 3.85% for the first 2 years after RS and declined to 1.3% thereafter. Multivariate analysis showed younger age, deep lesion location, and multiple pretreatment hemorrhages as significant predictors of posttreatment hemorrhage.Pretreatment hemorrhages led to permanent deficits in 41.4% of the cases with a single bleed and in 46.1% of cases with multiple bleeds. Only mild (modified Rankin Scale score 1) and a low rate of permanent neurological deficits were caused either by posttreatment hemorrhages (4.3%) or by radiation (2%).The rate of improvement in epilepsy was 84.9% after RS in patients with at least one seizure prior to treatment, not depending on the presence of hemorrhage or the time interval between presentation and treatment. Favorable outcome occurred in 81% of patients whose seizures were not controlled with antiepileptic medication prior to RS.CONCLUSIONSRadiosurgery for superficial CMs is safe and appears to be effective, offering a real treatment alternative to surgery for selected patients. Given their relatively benign natural history, superficial CMs require further study to verify the long-term benefit of RS over the lesions’ natural history.

LONG-TERM OUTCOME OF PATIENTS WITH MULTIPLE CEREBRAL CAVERNOUS MALFORMATIONS

Neurosurgery ◽

10.1227/01.neu.0000346269.59554.db ◽

2009 ◽

Vol 65 (3) ◽

pp. 450-455 ◽

Cited By ~ 27

Author(s):

Juri Kivelev ◽

Mika Niemelä ◽

Riku Kivisaari ◽

Reza Dashti ◽

Aki Laakso ◽

...

Keyword(s):

Family History ◽

De Novo ◽

Good Condition ◽

Neurological Deficits ◽

Cerebral Cavernous Malformations ◽

Cavernous Malformations ◽

Long Term Outcome ◽

History Of ◽

Abstract OBJECTIVE Multiple cerebral cavernous malformations (MCCMs) typically occur in patients with a family history of these lesions. Literature on MCCMs is scarce, and little is known about their natural history. METHODS Of 264 consecutive patients with cerebral cavernomas treated at the Department of Neurosurgery, Helsinki University Central Hospital, in the past 27 years, 33 patients had MCCMs. Lesions were categorized according to the Zabramski classification scale. Follow-up questionnaires were sent to all patients. Outcome was assessed using the Glasgow Outcome Scale, and amelioration of epilepsy was assessed using the Engel scale. All clinical data were analyzed retrospectively. RESULTS The mean age of patients at diagnosis was 44 years. Sex presentation was almost equal. Nine percent of all patients had a family history of the disease. Patients presented with epilepsy, acute headache, and focal neurological deficits. MCCMs were incidental findings in 2 patients. Altogether, 416 cavernomas were found: 70% supratentorial and 30% infratentorial. Fifteen patients had symptomatic hemorrhage before admission to our department. Surgery was performed on 18 patients. In most cases, the largest cavernoma was removed. Postoperatively, 1 patient experienced temporary hemiparesis, and another developed permanent motor dysphasia. No mortalities occurred. The mean follow-up time was 7.7 years. Twenty-six patients (79%) were in good condition. Among patients with epilepsy who underwent lesionectomy, 70% had an Engel class I outcome. On follow-up magnetic resonance imaging, 52 de novo cavernomas were found. CONCLUSION Surgical treatment of patients with MCCMs is safe. An extirpation of the clinically active cavernoma prevents further bleedings and improves outcome of epilepsy.

Systematic Review of Outcomes After Cochlear Implantation in Children With X-Linked Deafness-2

Otolaryngology ◽

10.1177/0194599820932138 ◽

2020 ◽

pp. 019459982093213

Author(s):

Joshua D. Smith ◽

Nour El-Kashlan ◽

Owen A. F. Darr ◽

Marc C. Thorne

Keyword(s):

Systematic Review ◽

Speech Perception ◽

Cochlear Implantation ◽

Auditory Perception ◽

Pure Tone Audiometry ◽

Cochrane Library ◽

Speech Performance ◽

The Mean ◽

Age Range

Objective Outcomes following cochlear implantation in children with X-linked deafness-2 are variable, resulting in challenges in appropriate preoperative counseling. To address this uncertainty, we performed a systematic review and synthesis of the literature on audiologic and speech outcomes after cochlear implantation in these patients to inform prognostic counseling. Data Sources PubMed, Embase, and Cochrane Library were queried for articles published between January 2000 and July 2019. Review Methods We performed a systematic review of all studies published between 2000 and 2019 that reported on (1) children with confirmed X-linked deafness-2 undergoing cochlear implantation and (2) formal assessment of hearing and/or speech capabilities postimplantation. Results Our initial database search yielded 313 articles. Fourteen articles met inclusion criteria. These studies reported on 61 children with X-linked deafness-2 who underwent implantation at a wide age range (1-29 years) for severe-profound sensorineural hearing loss of prelingual onset. The mean follow-up duration after implant activation was 32 months (range, 12-61). Outcome domains assessed at follow-up were heterogeneous, though each study employed at least 1 assessment of hearing (eg, pure tone audiometry), speech perception (eg, Early Speech Perception Test), or auditory perception (eg, Categories of Auditory Perception scores). In 10 of 14 studies, cochlear implantation afforded significant improvement in hearing and speech capabilities relative to preoperative performance or as compared with age-matched, normal-hearing controls. Conclusion The majority of studies demonstrate that cochlear implantation provides improvements in hearing and speech performance in patients with X-linked deafness-2. This information is valuable for decision making regarding cochlear implantation in these patients.

Clinical and Radiological Outcomes After Autologous Matrix-Induced Chondrogenesis Versus Microfracture of the Knee: A Systematic Review and Meta-analysis With a Minimum 2-Year Follow-up

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967120959280 ◽

2020 ◽

Vol 8 (11) ◽

pp. 232596712095928

Author(s):

Jun-Ho Kim ◽

Jae-Won Heo ◽

Dae-Hee Lee

Keyword(s):

Magnetic Resonance Imaging ◽

Systematic Review ◽

Magnetic Resonance ◽

Cochrane Library ◽

Resonance Imaging ◽

Level Of Evidence ◽

Common Procedure ◽

Subjective Score ◽

Background: Microfracture (MFx) is the most common procedure for treating chondral lesions in the knee; however, initial improvements decline after 2 years. Autologous matrix-induced chondrogenesis (AMIC) may overcome this shortcoming by combining MFx with collagen scaffolds. However, the outcomes of AMIC and MFx in the knee have not been compared. Purpose: To compare the clinical and radiological outcomes of AMIC and MFx over a minimum 2-year follow-up. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic search of the MEDLINE, Embase, and Cochrane Library databases identified studies of patients who underwent AMIC or MFx and that reported validated clinical outcome measure and/or radiological evaluation findings at a follow-up of ≥2 years. There were 2 reviewers who performed study selection, a risk of bias assessment, and data extraction. Results: Overall, 29 studies were included in this systematic review. The mean improvement on the Lysholm score, Tegner activity scale, and visual analog scale for pain did not differ significantly between the 2 procedures. The mean improvement on the International Knee Documentation Committee (IKDC) subjective score was significantly greater in the AMIC (45.9 [95% CI, 36.2-55.5]) than in the MFx (27.2 [95% CI, 23.3-31.1]) group ( P < .001). In addition, the mean magnetic resonance observation of cartilage repair tissue score was significantly higher in the AMIC (69.3 [95% CI, 55.1-83.5]) versus MFx (41.0 [95% CI, 27.3-54.7]) group ( P = .005), and the mean adequate defect filling rate on magnetic resonance imaging scans was significantly better in the AMIC (77.3% [95% CI, 66.7%-87.9%]) versus MFx (47.9% [95% CI, 29.2%-66.6%]) group ( P = .008) (odds ratio, 1.58 [95% CI, 1.07-2.33]). Conclusion: No significant differences in clinical outcomes, except for the IKDC subjective score, were found between the AMIC and MFx groups. Greater improvement in IKDC subjective scores and magnetic resonance imaging findings were seen in patients treated with AMIC compared with MFx at a minimum 2-year follow-up.

Use of antithrombotic agents in patients with intracerebral cavernous malformations

10.3171/2012.8.jns112050 ◽

2013 ◽

Vol 118 (1) ◽

pp. 43-46 ◽

Cited By ~ 16

Author(s):

Kelly D. Flemming ◽

Michael J. Link ◽

Teresa J. H. Christianson ◽

Robert D. Brown

Keyword(s):

High Risk ◽

Natural History ◽

Antiplatelet Agent ◽

Antithrombotic Agents ◽

Antithrombotic Agent ◽

Cavernous Malformations ◽

Risks And Benefits ◽

History Of ◽

Object The goal of this study was to determine the risk of using antithrombotic agents in patients with established intracerebral cavernous malformations (ICMs). Methods From a previously described cohort of 292 patients with radiographically defined ICMs, 40 required an antithrombotic after the ICM was diagnosed. Patients underwent follow-up to determine the incidence of hemorrhage. Results The mean age of these 40 patients was 62.4 years; there were 21 male and 19 female patients. Five (12.5%) of the 40 patients initially presented with hemorrhage and 4 (10%) had multiple ICMs. Of these patients, 32 were placed on an antiplatelet agent alone, 6 on an anticoagulant alone, and 2 were placed on both. In patients necessitating any antithrombotic agent, 1 patient developed a prospective hemorrhage over the 258 person-years of follow-up (prospective hemorrhage rate 0.41% per person-year). Conclusions Antithrombotics likely do not precipitate hemorrhage in patients with known ICMs. However, caution should be exercised in the use of antithrombotics in patients with ICMs at high risk for hemorrhage. The risks and benefits of antithrombotics in each situation should be carefully weighed against the natural history of ICM.