Our aim was to report the long-term clinical and imaging outcomes of ≤15-year-old children treated for ruptured or symptomatic cerebral aneurysms and to identify prognostic factors for clinical outcome, recurrence, and rebleeding.
We retrospectively identified all pediatric cases of cerebral aneurysm from 2000 to 2015 and then prospectively evaluated long-term occlusion using brain MRI and clinical outcome measures: outcome was considered favorable if King’s Outcome Scale for Childhood Head Injury score was ≥5. We performed univariate analysis and logistic binary regression to identify variables associated with clinical and imaging outcomes.
Fifty-one children (aged 8.5 ± 1.1 years [mean ± SD], with 37 ruptured and 14 symptomatic aneurysms) were included, and endovascular treatments (84%) or microsurgical procedures (16%) were performed. Despite a 19.6% death rate, at a mean follow-up of 8.3 years, 35 children (68.6%) had a favorable outcome. Annual bleeding and aneurysm recurrence rates were 1.4% ± 1.1% and 2.6% ± 1.8%, respectively. Cerebral ischemia, whether initial or delayed within the first month, was predictive of poor clinical outcome in multivariate analysis (odds ratio: 25; 95% confidence interval: 0.43–143; P < .0001), whereas aneurysm size >5 mm was the only factor associated with recurrence (odds ratio: 14.6; 95% confidence interval: 2.4–86.1; P = .003).
Two-thirds of studied ≤15-year-old children suffering from ruptured or symptomatic cerebral aneurysms had long-term favorable outcome. Annual bleeding and aneurysm recurrence rates have shown to be low after endovascular or surgical treatment. Long-term imaging follow-up helps to depict aneurysm recurrence or de novo aneurysm formation and to prevent rebleeding.
Cerebral arterial aneurysms are extremely rare in children in comparison with adults. Long-term clinical and imaging follow-up studies on pediatric cerebral aneurysms are scarce, especially in young patients under 15 years old that are managed endovascularly.
We demonstrated that two-thirds of children suffering from a ruptured or symptomatic cerebral aneurysm had a long-term favorable outcome. Annual bleeding and aneurysm recurrence rates are low after treatment. Long-term imaging follow-up is mandatory to detect aneurysm recurrence and de novo aneurysm.
Cerebral arterial aneurysms are extremely rare in children compared with adults, accounting for <4% of all intracranial aneurysms.1,–3 Endovascular treatment (EVT) and surgical clipping are treatment options; the transarterial embolization with coiling procedure has increased in recent years. Long-term clinical and imaging follow-up studies on pediatric cerebral aneurysms are scarce, especially in young patients under 15 years old or in current endovascular cohorts.4,5
Our aim here was to report the long-term clinical and imaging outcomes of ≤15-year-old children taken in charge from the year 2000 to 2015 and treated for ruptured or symptomatic cerebral aneurysms as well as to identify prognostic factors for clinical outcome, recurrence, and rebleeding.
Methods
Study Design and Participants
We performed this study according to the strengthening the reporting of observational studies in epidemiology (STROBE) statement6 and French legislation, and because the study implied retrospective analysis of anonymized data collected as part of routine clinical care, it did not require formal approval by an ethics committee nor patient written informed consent. We informed each patient of his or her participation in the study. The study was a multicenter retrospective pediatric study (Bicêtre Hospital, Necker Hospital, Saint-Anne Hospital, Paris, France) that included all consecutive children treated between 2000 and 2015. Inclusion criteria were (1) intracranial arterial aneurysm (IAA) and (2) age <18 years. We excluded patients with (1) arteriovenous malformation–related aneurysms, (2) vein of Galen aneurysmal malformation, and (3) mycotic pseudoaneurysm, because they correspond to different diseases.
Clinical and Imaging Parameters
We extracted clinical and demographic data from patient charts. We registered the World Federation of Neurological Surgeons (WFNS) grade for aneurysmal subarachnoid hemorrhage (SAH) and the Fisher’s score at onset.7,8 We defined aneurysm size and location at onset on magnetic resonance angiography, computed tomography–angiography, or digital subtraction angiography (DSA) obtained at admission. They were then classified as saccular or acute dissecting and/or fusiform aneurysms.9,10 Two neuroradiologists came to a common agreement concerning posttreatment as well as classifying long-term aneurysm occlusion using magnetic resonance angiography or DSA, according to the 3-grade Raymond classification: grade 1, no contrast filling; grade 2, neck remnant; and grade 3, opacification of the aneurysmal sac.11
Treatment Strategy
Except in cases requiring emergency intracranial hemorrhage evacuation (Glasgow Coma Scale score <8, posterior fossa intracranial hemorrhage [ICH], or with mass effect), the treatment modality was decided at a multidisciplinary consensus meeting including pediatric neurosurgeons and pediatric interventional neuroradiologists. For children in good clinical condition in which surgical ICH evacuation was not indicated, EVT was considered as first-line therapy. In cases of EVT failure, surgical clipping was performed.
Follow-up
We collected clinical and imaging follow-up data during hospitalization and follow-up DSA during an external consultation or by telephone interviews. We contacted all patients to undergo a physical examination and brain magnetic resonance angiography. We made repeated telephone calls to contact missing patients and their families (family, relatives, and general physician). When appropriate, we collected causes of death. The total number of months of clinical and imaging follow-up for each patient was recorded. Clinical outcome was defined according to the King’s Outcome Scale for Childhood Head Injury (KOSCHI).12 Favorable clinical outcome was defined as a KOSCHI score ≥5.
Statistics
Associations between variables were analyzed by Fisher’s exact test or χ2 test. The distribution of categorical variables was described by frequencies and percentages, continuous and normally distributed variables by means and SDs, and continuous and non-normally distributed variables by medians and interquartile range. Predictive factors for unfavorable outcome, aneurysm recurrence, or rebleeding were tested by univariate statistics by using analysis of variance and χ2 or Fisher’s exact tests, as appropriate. According to the number of pairwise comparisons of interest, type 1 error was adjusted by using the Bonferroni multiple comparison adjustment. For example, α level of .05 divided by 17 comparisons yielded an adjusted α of .003; thus, the statistical significance level was set at P = .003. All variables with a significant association in the univariate analyses after adjustment were entered into a multiple logistic regression model by using backward elimination procedures to analyze potential predictors of unfavorable outcome. Statistical analyses were performed using Stata version 11 (Stata Corp, College Station, TX).
Results
Clinical Presentation
We present child and aneurysm baseline characteristics in the supplemental Table 1. Over the study period, 51 children (73 aneurysms; mean age ± SD: 8.5 ± 1.1 years; interquartile range: 5.1–11.1 years) met our inclusion criteria.
Baseline Patient and Aneurysm Characteristics
| Symptomatic Patient Characteristics | n (%) or Mean ± SD |
|---|---|
| Patients | 51 |
| Male sex | 35 (68.6) |
| Age, y | 8.5 ± 1.1 |
| Vascular disease | 5 (9.8) |
| Sickle cell disease | 4 (7.3) |
| Genetic dysmorphic syndrome | 3 (5.8) |
| Familial history of aneurysm | 2 (4) |
| Clinical presentation | |
| SAH | 37 (72.5) |
| Initial coma (GCS score <8) | 7 (13.7) |
| WFNS score 3–5 | 18 (35.3) |
| Fisher’s score 4–5 | 26 (50.9) |
| Headaches | 9 (17.6) |
| Epilepsy | 1 (1.9) |
| Cranial nerve palsy | 2 (3.9) |
| Ischemic stroke | 2 (3.9) |
| Baseline treated aneurysm characteristics | 51 |
| Aneurysm type | |
| Saccular | 31 (60.7) |
| Fusiform or dissecting | 20 (29.3) |
| Ruptured | 37 (72.5) |
| Patients with multiple aneurysms | 8 (15.6) |
| Fundus size, mm | 9.9 (7.5) |
| <10 | 30 (58.8) |
| 10–25 | 18 (34.6) |
| >25 | 3 (5.8) |
| Anterior circulation location | 36 (70.5) |
| Middle cerebral artery | 11 (21.5) |
| Anterior complexa | 4 (7.3) |
| Internal carotid arteryb | 21 (41.2) |
| Posterior circulation location | 15 (29.5) |
| Posterior communicating artery | 3 (5.4) |
| Posterior cerebral artery | 6 (10.9) |
| Vertebral-basilar artery | 4 (7.3) |
| Superior cerebellar artery | 2 (3.6) |
| Symptomatic Patient Characteristics | n (%) or Mean ± SD |
|---|---|
| Patients | 51 |
| Male sex | 35 (68.6) |
| Age, y | 8.5 ± 1.1 |
| Vascular disease | 5 (9.8) |
| Sickle cell disease | 4 (7.3) |
| Genetic dysmorphic syndrome | 3 (5.8) |
| Familial history of aneurysm | 2 (4) |
| Clinical presentation | |
| SAH | 37 (72.5) |
| Initial coma (GCS score <8) | 7 (13.7) |
| WFNS score 3–5 | 18 (35.3) |
| Fisher’s score 4–5 | 26 (50.9) |
| Headaches | 9 (17.6) |
| Epilepsy | 1 (1.9) |
| Cranial nerve palsy | 2 (3.9) |
| Ischemic stroke | 2 (3.9) |
| Baseline treated aneurysm characteristics | 51 |
| Aneurysm type | |
| Saccular | 31 (60.7) |
| Fusiform or dissecting | 20 (29.3) |
| Ruptured | 37 (72.5) |
| Patients with multiple aneurysms | 8 (15.6) |
| Fundus size, mm | 9.9 (7.5) |
| <10 | 30 (58.8) |
| 10–25 | 18 (34.6) |
| >25 | 3 (5.8) |
| Anterior circulation location | 36 (70.5) |
| Middle cerebral artery | 11 (21.5) |
| Anterior complexa | 4 (7.3) |
| Internal carotid arteryb | 21 (41.2) |
| Posterior circulation location | 15 (29.5) |
| Posterior communicating artery | 3 (5.4) |
| Posterior cerebral artery | 6 (10.9) |
| Vertebral-basilar artery | 4 (7.3) |
| Superior cerebellar artery | 2 (3.6) |
GCS, Glasgow Coma Scale.
Included anterior communicating artery and A1-A2 junction aneurysms.
Included ophthalmic artery region, supraclinoid, superior hypophyseal artery, and internal carotid artery bifurcation.
Thirty-seven children (72.5%) presented with SAH from a ruptured aneurysm. We show WFNS grade and Fisher’s scores in Table 1.
Fourteen patients (27.5%) had a symptomatic unruptured aneurysm (9 thunderclap headaches without SAH, 1 epilepsy or seizure, 2 partial third nerve deficits, and 2 related to ischemic stroke).
Five children (9.8%) had a vascular disease, 3 (5.8%) had a genetic dysmorphic syndrome (dwarfism or unlabeled), and 4 (7.8%) had a sickle cell disease. Two children (4%) had at least 1 first-degree family relative with IAA.
Initial Treatment
Clinical Outcome
Mean clinical follow-up was 8.3 years (range: 12 months–19.5 years, 423.3 patient years), with favorable outcome encountered in 35 out of 51 (68.6%) children (31 and 4 had KOSCHI 5B and KOSCHI 5A, respectively). Unfavorable outcome included 1 child with moderate disability (KOSCHI 4), 1 with severe disability (KOSCHI 3), 4 who presented a vegetative state (KOSCHI 2), and 10 who died (KOSCHI 1).
Among 37 SAH patients, 23 children had a favorable outcome. Among the 14 unfavorable outcomes, 10 children died within the first month of SAH onset (n = 9; mean onset-to-death delay: 12 days) or from the bleeding of an untreated additional aneurysm (n = 1; annual case fatality rate from rebleeding: 0.2% ± 0.1%). Rebleeding occurred in 6 patients (annual bleeding rate: 1.4% ± 1.1%; median delay: 26 months; range: 1.2–36 months), 4 from aneurysm recurrence, 1 from a de novo aneurysm, and 1 from an additional aneurysm. We did not identify risk factors for rebleeding in the univariate survival analysis (data not shown).
In univariate analysis (Table 2), unfavorable outcome was associated with aneurysm size of >5 mm (P = .04), ischemic stroke (P = .0001), and initial coma (P = .005). Ischemic stroke was the only factor independently associated with unfavorable outcome (odds ratio [OR]: 24.7; 95% confidence interval [CI]: 4.3–142.1; P < .0001). Acute ischemic strokes recorded in our series were due to dissecting aneurysms and occurred via perforating branches from the dissection or in the vascular territory downstream. Ischemic stroke (OR: 8.6; 95% CI: 1.4–53.1; P = .003), coma at onset (OR: 16.7; 95% CI: 2.3–115.1; P = .004), and rebleeding (OR: 9.2; 95% CI: 3.7–38.1; P = .02) were independent risk factors of death.
Clinical and Aneurysmal Predictive Factors for Death, Unfavorable Outcome, Rebleeding, and Recurrent Aneurysm (P Values Were Calculated by the Log-Rank Test)
| Baseline Clinical and Aneurysm Characteristics | Univariate Analysis, P | Multivariate Analysis, OR (95% CI) P | ||||||
|---|---|---|---|---|---|---|---|---|
| Death | Unfavorable Outcome | Aneurysm Rebleeding | Aneurysm Recurrence | Death | Unfavorable Outcome | Aneurysm Rebleeding | Aneurysm Recurrence | |
| Sex | .58 | .99 | .60 | .23 | — | — | — | — |
| Age, y | ||||||||
| <2 | .353 | .118 | .202 | .328 | — | — | — | — |
| <5 | .113 | .099 | .908 | .169 | — | — | — | — |
| <8 | .486 | .126 | .640 | .236 | — | — | — | — |
| <12 | .714 | .527 | .706 | .925 | — | — | — | — |
| SAH | .08 | .13 | .40 | .18 | — | — | — | — |
| Coma | .004a | .005a | .738 | .670 | 16.7 (2.3–115.1) .004a | 4.4 (0.6–27.0) .137 | — | — |
| Multiple aneurysms | .11 | .70 | .30 | .13 | — | — | — | — |
| Posterior circulation aneurysm | .11 | .39 | .15 | .34 | — | — | — | — |
| Aneurysm size >5 mm | .03a | .04a | .30 | .002a | 1.0 (0.1–2.7) .99 | 0.17 (0.1–2.21) .179 | — | 14.6 (2.4–86.0) .003a |
| Aneurysm form | ||||||||
| Saccular | .46 | .15 | .41 | .23 | — | — | — | — |
| Fusiform or dissecting | .63 | .66 | .57 | .73 | — | — | — | — |
| Complications | ||||||||
| Hydrocephalus | .67 | .68 | .86 | .73 | — | — | — | — |
| Stroke | .018a | .0001a | .70 | .29 | 8.6 (1.4–53.1) .003a | 24.7 (4.3–142.1) <.0001a | — | — |
| Vasospasm | .46 | .99 | .79 | .05 | — | — | — | — |
| Rebleeding | .016a | .06 | — | .52 | 9.2 (3.7–38.1) .02a | — | — | — |
| Baseline Clinical and Aneurysm Characteristics | Univariate Analysis, P | Multivariate Analysis, OR (95% CI) P | ||||||
|---|---|---|---|---|---|---|---|---|
| Death | Unfavorable Outcome | Aneurysm Rebleeding | Aneurysm Recurrence | Death | Unfavorable Outcome | Aneurysm Rebleeding | Aneurysm Recurrence | |
| Sex | .58 | .99 | .60 | .23 | — | — | — | — |
| Age, y | ||||||||
| <2 | .353 | .118 | .202 | .328 | — | — | — | — |
| <5 | .113 | .099 | .908 | .169 | — | — | — | — |
| <8 | .486 | .126 | .640 | .236 | — | — | — | — |
| <12 | .714 | .527 | .706 | .925 | — | — | — | — |
| SAH | .08 | .13 | .40 | .18 | — | — | — | — |
| Coma | .004a | .005a | .738 | .670 | 16.7 (2.3–115.1) .004a | 4.4 (0.6–27.0) .137 | — | — |
| Multiple aneurysms | .11 | .70 | .30 | .13 | — | — | — | — |
| Posterior circulation aneurysm | .11 | .39 | .15 | .34 | — | — | — | — |
| Aneurysm size >5 mm | .03a | .04a | .30 | .002a | 1.0 (0.1–2.7) .99 | 0.17 (0.1–2.21) .179 | — | 14.6 (2.4–86.0) .003a |
| Aneurysm form | ||||||||
| Saccular | .46 | .15 | .41 | .23 | — | — | — | — |
| Fusiform or dissecting | .63 | .66 | .57 | .73 | — | — | — | — |
| Complications | ||||||||
| Hydrocephalus | .67 | .68 | .86 | .73 | — | — | — | — |
| Stroke | .018a | .0001a | .70 | .29 | 8.6 (1.4–53.1) .003a | 24.7 (4.3–142.1) <.0001a | — | — |
| Vasospasm | .46 | .99 | .79 | .05 | — | — | — | — |
| Rebleeding | .016a | .06 | — | .52 | 9.2 (3.7–38.1) .02a | — | — | — |
—, not applicable.
Statistically significant.
Imaging Outcome
Forty children were prospectively managed on imaging (DSA, n = 9; 1.5 Tesla, n = 17; 3.0 Tesla, n = 14) for a mean follow-up period of 7.1 years (range: 6 months–19.5 years; 312.4 patient years).
Eight aneurysm recurrences occurred in 8 patients (EVT, n = 7 [19%]; surgery, n = 1 [14%]; mean delay: 1.7 ± 1.4 years; annual aneurysmal recurrence rate: 2.6% ± 1.8%). No significant association was found between recurrence and aneurysm type (Table 2). The annual re-treatment rate was 1.2% ± 1.00% (5 re-treatments; EVT, n = 3; surgery, n = 2), and the annual de novo aneurysm rate was 0.7% ± 0.4% (2 IAAs in 2 patients). Aneurysm size >5 mm was independently associated with aneurysm recurrence (OR: 14.6; 95% CI: 2.4–86.0; P = .003).
Discussion
In this study of ≤15-year-old children treated for ruptured or symptomatic IAA, a favorable outcome occurred in two-thirds of cases. The annual bleeding rate after treatment, re-treatment rate, and aneurysmal recurrence rate were, respectively, 1.4%, 1.2%, and 2.6%. Annual de novo aneurysm rate, mainly based on 3 Tesla MRI examinations, was 0.7%.
The current study focused on patients treated after the year 2000 and therefore concerned recent management strategy. Indeed, a majority of pediatric IAA studies in the literature include few patients, treated often over several decades. The current study significantly differs from the previous studies, and we provide additional information on outcomes after symptomatic cerebral aneurysms in children (summarized in Table 3). First, we focused on a young population, for >25% of our population was <5 years old. Our study showed favorable outcome for over two-thirds of cases. Concerning the risk of annual recurrence, in our series it was 2.6%, a rate similar to one observed in the adult series of aneurysms.2,3 In contrast, the Finnish cohort reported a lower annual rate of aneurysm recurrence of 0.6% in the pediatric patients.4 In this largest long-term cohort study (1939–2010), Koroknay-Pál et al4 described 114 older children (mean age >14 years) that could, in part, explain the difference in results (Table 3).
Detailed Characteristics of Previous Studies With Follow-up ≥3 Years
| Authors | Study | Setting, Enrollment | Median Year of Treatment | No. patients, No. aneurysms | Mean Age, y | Ruptured, Symptomatic, Incidental | Type of EVT: Elective, Nonelectivea | Type of Surgery: Clipping, Otherb | Fusiform, Saccular | Mean Clinical FU, y | Mean Imaging FU | Annual Recurrence Rate, % | Annual De Novo or Enlarging Rate of Untreated Aneurysm, % |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sanai et al13 | Observational, United States | Single center, retrospective | 1997–2003 | 32, 43 | 11.7 | 7, 13, 12 | 12, 14 | 8, 9 | 21, 22, unknown, unknown | 5.7 | 5.7 | 1.8c | 2.4c |
| Hetts et al2,14 | Observational, United States | Single center, retrospective | 1981–2010 | 77, 103 | 12.0 | 25, 29, 6 | 20, 11 | 19, 10 | 31, 47, 12, 15 | Unknown | 3.0c | Unknown | 3.7c |
| Kakarla et al3 | Observational, United States | Single center, retrospective | 1989–2005 | 48, 72 | 12.3 | 11, 35, 26 | 0 | 48, 24 | 28, 32, 5, 7 | 4.9 | 4.5 | 2.6 | 7.8 |
| Koroknay-Pál et al4,5 | Observational, Finland | Single center, retrospective | 1937–2009 | 114, 130 | 14.5 | 89, 18, 7 | 3, 0 | 60, 20 | Unknown | Unknown | 34.0d | 0.6 | 1.3 |
| Saraf et al15 | Observational, Finland | Single center, retrospective | 1998–2010 | 23, 28 | 13.0 | 14, unknown, unknown | 10, 10 | 0 | 17, 6, 5, unknown | 3.0 | 3.0 | 1.4 | Unknown |
| Present study | Observational, France | Multicenter, prospective | 2000–2015 | 51, 73 | 8.5 | 37, 14, 0 | 43 | 8 | 31, 20, 0, 0 | 8.3 | 7.1 | 2.6 | 0.7 |
| Authors | Study | Setting, Enrollment | Median Year of Treatment | No. patients, No. aneurysms | Mean Age, y | Ruptured, Symptomatic, Incidental | Type of EVT: Elective, Nonelectivea | Type of Surgery: Clipping, Otherb | Fusiform, Saccular | Mean Clinical FU, y | Mean Imaging FU | Annual Recurrence Rate, % | Annual De Novo or Enlarging Rate of Untreated Aneurysm, % |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sanai et al13 | Observational, United States | Single center, retrospective | 1997–2003 | 32, 43 | 11.7 | 7, 13, 12 | 12, 14 | 8, 9 | 21, 22, unknown, unknown | 5.7 | 5.7 | 1.8c | 2.4c |
| Hetts et al2,14 | Observational, United States | Single center, retrospective | 1981–2010 | 77, 103 | 12.0 | 25, 29, 6 | 20, 11 | 19, 10 | 31, 47, 12, 15 | Unknown | 3.0c | Unknown | 3.7c |
| Kakarla et al3 | Observational, United States | Single center, retrospective | 1989–2005 | 48, 72 | 12.3 | 11, 35, 26 | 0 | 48, 24 | 28, 32, 5, 7 | 4.9 | 4.5 | 2.6 | 7.8 |
| Koroknay-Pál et al4,5 | Observational, Finland | Single center, retrospective | 1937–2009 | 114, 130 | 14.5 | 89, 18, 7 | 3, 0 | 60, 20 | Unknown | Unknown | 34.0d | 0.6 | 1.3 |
| Saraf et al15 | Observational, Finland | Single center, retrospective | 1998–2010 | 23, 28 | 13.0 | 14, unknown, unknown | 10, 10 | 0 | 17, 6, 5, unknown | 3.0 | 3.0 | 1.4 | Unknown |
| Present study | Observational, France | Multicenter, prospective | 2000–2015 | 51, 73 | 8.5 | 37, 14, 0 | 43 | 8 | 31, 20, 0, 0 | 8.3 | 7.1 | 2.6 | 0.7 |
FU, follow-up
Includes parent vessel occlusion with coils or glue and flow reversal.
Includes trapping, wrapping, ligation, bypass, or high-flow bypass.
Recalculated from published data.
Follow-up of the subgroup of 1-y survivors (n = 88).
Secondly, as our study concerns children treated recently, 84% of treatments were endovascular, a rate similar to the ones seen in the recent adult cohorts.2,4,14,16 Conversely, in the study performed by Koroknay-Pál et al4 on older children, 98% underwent surgical clipping, which may also explain our different results (Table 3).
With aneurysm formation being extremely rare in children, an underlying vascular disease is often suspected or identified, for instance, sickle cell disease in the present series or in the literature.17 However, in our series and as previously reported, no connective tissue disorders were diagnosed.4
The annual de novo aneurysm rate, mainly based on 3 Tesla MRI examinations, was low, estimated at 0.7%, whereas the annual rebleeding rate was 1.4%. In addition, these rates seem to compare favorably with adult cohorts.18,19
Furthermore, the good neurologic outcome rate reported here is higher than previously described.2,4,16 This may be explained by a higher rate of treatment of ruptured aneurysms than before and by the major advances in neurointensive care because outcome was not significantly worsened by initial coma.16 However, the long-term rate of aneurysm-related death was not as high as reported in the Koroknay-Pál et al5 series, who described 26% aneurysm-related death.
A 10% to 19% excess of mortality 20 years after diagnosis in 1-year survivors of pediatric SAH was described.4 Because this mortality is mainly aneurysm related (76%) after rebleeding from a recurrent or bleeding from a de novo aneurysm, long-term imaging follow-up is mandatory in children. We showed effectiveness of EVT with annual bleeding and aneurysm recurrence rates similar to those previously described for pediatric microsurgery or in adult endovascular series.3,4,14 We identified a significantly higher recurrence rate in cases of larger aneurysms, a well-known association in adults,20 not previously described in children. Interestingly, the 40% rate of fusiform or dissecting aneurysms did not influence this higher recurrence rate. We found a low de novo aneurysm rate, a finding that may be due to the short follow-up compared with the Finnish cohort.5
Even if safe and efficacious, the long-term durability of endovascular embolization remains a concern, especially in ruptured aneurysms, where stent-assisted coiling or a flow diverter is rarely used. Indeed, in unruptured aneurysms, this recurrence rate ranges from 7% to 27% and increases to 17% to 52% in ruptured aneurysms.11,21,–26 However, among our 7 patients treated surgically, 1 had a recurrence and subsequently bled and died. It was an acute dissecting aneurysm, initially misdiagnosed as a saccular carotid aneurysm: no mural hematoma, double lumen, or intimal flap were identified on angio-imaging (computed tomography–angiography and DSA) performed before surgery. The diagnosis was made during surgery, and although wrapping was successful to reconstruct the artery, it failed to prevent an early recurrence and fatal rebleeding. Because no guidelines for the treatment of ruptured dissecting aneurysms are available, at least early posttreatment follow-up imaging is mandatory to rule out fresh recurrence, which would indicate re-treatment to prevent new bleeding.
One limitation of this study is its retrospective design, although all our patients were prospectively registered in dedicated neurovascular databases. IAA remains rare, and randomized pediatric studies are probably unrealistic. We were unable to perform analysis on the basis of the treatment modality because only 8 children were in the surgical group. In addition, surgery was mainly performed in cases requiring emergency intracranial hemorrhage evacuation, precluding any outcome comparison with EVT. Researchers conducting further studies should help to provide more reliable data as well as a better understanding of this rare but sometimes devastating disease.
Conclusions
In this series, ruptured intracranial aneurysms are still associated with a high mortality rate in the acute phase in pediatric patients; however, a favorable long-term outcome is seen in two-thirds of cases. Despite a low annual rebleeding or aneurysm recurrence rate, lifelong clinical and imaging follow-up is mandatory to detect aneurysm recurrence and de novo aneurysm formation.
Drs Amelot, Blauwblomme, Naggara, and Saliou conceptualized and designed the study, conducted the initial analyses, and drafted the initial manuscript; Drs Alias, Boulouis, Ozanne, Benichi, Zerah, and Aghakhani drafted and reviewed the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
FUNDING: No external funding.
Comments
RE: Letter: Reply comment on: Long-term Outcomes of Cerebral Aneurysms in Children
Aymeric Amelot,1,2 MD-PhD; Guillaume Saliou,3,4 MD-PhD; Thomas Blauwblomme,2 MD-PhD; Olivier Naggara,5,6 MD-PhD
Affiliations: 1: Neurosurgery Department, La Pitié-Salpétrière Hospital, Paris, France; Université Paris Sorbonne, 2: Pediatric Neurosurgery Department, Necker Hospital for Sick Children , Paris, France; Université Paris Descartes, 3: Neuroradiology Department, Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France, 4: Neuroradiology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switerzland, 5: Pediatric Radiology Department, Necker Hospital for Sick Children, Paris, France; Université Paris Descartes, 6: Neuroradiology Department, Sainte-Anne Hospital, Paris, France; Université Paris Descartes, INSERM UMR S894.
Address correspondence to: Aymeric Amelot, M.D., Ph.D., Department of Neurosurgery, Groupe Hospitalier Universitaire de la Pitié-Salpêtrière, 47-83, Boulevard de l’Hôpital 75013 Paris, France. Email: aymmed@hotmail.fr, tel.: 00 32 1 42163303, Fax: 00 32 1 42163342
Source of Funding: None.
Financial Disclosure: The authors declare no institutional financial interest in any of the drugs, materials or devices described in the manuscript.
Conflict of Interest: The authors declare no conflicts of interest.
Abbreviations:
IAA: Intracranial Arterial Aneurysm
SAH: Subarachnoid Hemorrhage
DSA: Digital Subtraction Angiography
UIA: Unruptured Intracranial Arterial Aneurysm
Contributors’ Statements:
A. Amelot, T. Blauwblomme, O. Naggara and G. Saliou conceptualized and designed the reply and approved the final manuscript as submitted.
To the Editor:
We would like to thank Prof. Feng and collaborators for their interest in our study on long term follow-up of pediatric cerebral aneurysms1 and for their observations2. We described fifty-one children with cerebral aneurysm in our investigation, mainly treated by endovascular therapy, in two centers over 15 years and with a mean clinical and imaging follow-up of >8 years. Due to the rarity of pediatric cerebral aneurysms, our study corresponds to one of the most important series published to date. Feng et al. cited some references relating to adult studies of cerebral aneurysms in their comment In our opinion, comparison between adult and pediatric aneurysms is not optimal as aneurysms are extremely rare in children, with an estimated prevalence of 10-100 per million, whereas they are encountered in nearly 3% of adults. In addition, profound differences, regarding presentation, etiology, type of treatment and outcome, as shown in our study, precludes any comparison between adult- and childhood aneurysms. We identified initial clinical status, assessed using the Glasgow Coma Scale, as a long-term prognostic factor, while neither the amount of blood in the subarachnonid spaces, assessed using the Fisher scale, nor hydrocephalus were associated with unfavorable outcome. We acknowledge that due to the small sample size, the statistical power was low for identification of risk factors after multiple regression analyses. We agree with Feng et al. that a distinct analysis of clinical outcome in ruptured and unruptured aneurysms after endovascular treatment is pertinent in the adult population. However, in our pediatric population, we choose not to distinguish outcome based on rupture status as unruptured lesions were symptomatic lesions, discovered in the work-up of severe headaches (n=9), compressive cranial nerve palsy (n=2), epilepsy (n=1) and ischemic stroke due to migration of an intra-aneurysmal thrombus (n=2). In addition, we focused our study on long-term imaging follow-up, with endpoints such as index aneurysm recurrence or de novo aneurysm occurrence for which the ruptured/unruptured status was not described as a risk factor. Until clear-cut data become available demonstrating that pediatric aneurysms are similar to adult aneurysms, we believe we should continue to consider the course and natural history of pediatric cerebral aneurysms as specific.
References
1. Feng X, Wang D. RE: Long-term Outcomes of Cerebral Aneurysms in Children. 2019 May 8. pii: e20183036. doi: 10.1542/peds.2018-3036.
2. Amelot A, Saliou G, Benichi S et al. Long-term Outcomes of Cerebral Aneurysms in Children. Pediatrics. 2019 May 8. pii: e20183036. doi: 10.1542/peds.2018-3036.
Disclosure
The authors declare no conflicts of interest
RE: Long-term Outcomes of Cerebral Aneurysms in Children
TO THE EDITOR: I read with interest the article by Aymeric Amelot et al.1 (Long-term Outcomes of Cerebral Aneurysms in Children). They reported the long-term clinical and imaging outcomes of <15-year-old children treated for ruptured or symptomatic cerebral aneurysms and to identify prognostic factors for clinical outcome, recurrence, and rebleeding. They found that 68.6% children had a favorable outcome. As the article mentioned, studies based on 37 ruptured and 14 symptomatic aneurysms, and endovascular treatments (84%) or microsurgical procedures (16%) were performed. The series of this study and the number of cases of neurological worsening was so small that the statistical power was not sufficient enough to extract the true primary risk factor after multiple regression analyses. In addition, it is not recommended to analyze the clinical outcome of ruptured and unruptured aneurysms together because the comparability of the two different statues of aneurysms is relatively low, and many of them have reported their vast differences. In addition, there are many different factors affecting the prognosis of ruptured or unruptured aneurysms. For ruptured aneurysms, the most important factor affecting the prognosis of patients may be the clinical status of SAH at the time of onset (such as the Hunt Hess score, World Federation of Neurosurgical Societies (WFNS)) and the timing of treatment1,2. For unruptured aneurysms, the clinical prognosis is affected to some extent by surgery-related complications and recurrence of aneurysms. Therefore, in addition to the results already presented in the paper, the authors should separately discuss the clinical prognosis of ruptured and unruptured aneurysms and their influencing factors. Finally, the study retrospectively identified all pediatric cases of cerebral aneurysm from 2000 to 2015. It means that the research period has spanned 15 years of rapid development of endovascular treatment. Is the prognosis of aneurysms in children different after improvement of skills and strategy?3,4 So, it would be better to add relevant analysis and discussion to the article.
Reference
1. Jaja Blessing N R,Saposnik Gustavo,Lingsma Hester F et al. Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study.[J] .BMJ, 2018, 360: j5745.
2. Zuo Qiao,Yang Pengfei,Lv Nan et al. Safety of coiling with stent placement for the treatment of ruptured wide-necked intracranial aneurysms: a contemporary cohort study in a high-volume center after improvement of skills and strategy.[J] .J. Neurosurg., 2018, undefined: 1-7.
3. Rubbert Christian,Patil Kaustubh R,Beseoglu Kerim et al. Prediction of outcome after aneurysmal subarachnoid haemorrhage using data from patient admission.[J] .Eur Radiol, 2018, 28: 4949-4958.
4. Pierot Laurent,Cognard Christophe,Anxionnat René et al. Remodeling technique for endovascular treatment of ruptured intracranial aneurysms had a higher rate of adequate postoperative occlusion than did conventional coil embolization with comparable safety.[J] .Radiology, 2011, 258: 546-53.
RE: Long-term Outcomes of Cerebral Aneurysms in Children
TO THE EDITOR: I read with interest the article by Aymeric Amelot et al.1 (Long-term Outcomes of Cerebral Aneurysms in Children). They reported the long-term clinical and imaging outcomes of <15-year-old children treated for ruptured or symptomatic cerebral aneurysms and to identify prognostic factors for clinical outcome, recurrence, and rebleeding. They found that 68.6% children had a favorable outcome. As the article mentioned, studies based on 37 ruptured and 14 symptomatic aneurysms, and endovascular treatments (84%) or microsurgical procedures (16%) were performed. The series of this study and the number of cases of neurological worsening was so small that the statistical power was not sufficient enough to extract the true primary risk factor after multiple regression analyses. In addition, it is not recommended to analyze the clinical outcome of ruptured and unruptured aneurysms together because the comparability of the two different statues of aneurysms is relatively low, and many of them have reported their vast differences. In addition, there are many different factors affecting the prognosis of ruptured or unruptured aneurysms. For ruptured aneurysms, the most important factor affecting the prognosis of patients may be the clinical status of SAH at the time of onset (such as the Hunt Hess score, World Federation of Neurosurgical Societies (WFNS)) and the timing of treatment1,2. For unruptured aneurysms, the clinical prognosis is affected to some extent by surgery-related complications and recurrence of aneurysms. Therefore, in addition to the results already presented in the paper, we recommend separately discussing the clinical prognosis of ruptured and unruptured aneurysms and their influencing factors. Finally, the study retrospectively identified all pediatric cases of cerebral aneurysm from 2000 to 2015. It means that the research period has spanned 15 years of rapid development of endovascular treatment. Is the prognosis of aneurysms in children different after improvement of skills and strategy?3,4 So, we think it would be better to add relevant analysis and discussion to the article.
Reference
1. Jaja Blessing N R,Saposnik Gustavo,Lingsma Hester F et al. Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study.[J] .BMJ, 2018, 360: j5745.
2. Zuo Qiao,Yang Pengfei,Lv Nan et al. Safety of coiling with stent placement for the treatment of ruptured wide-necked intracranial aneurysms: a contemporary cohort study in a high-volume center after improvement of skills and strategy.[J] .J. Neurosurg., 2018, undefined: 1-7.
3. Rubbert Christian,Patil Kaustubh R,Beseoglu Kerim et al. Prediction of outcome after aneurysmal subarachnoid haemorrhage using data from patient admission.[J] .Eur Radiol, 2018, 28: 4949-4958.
4. Pierot Laurent,Cognard Christophe,Anxionnat René et al. Remodeling technique for endovascular treatment of ruptured intracranial aneurysms had a higher rate of adequate postoperative occlusion than did conventional coil embolization with comparable safety.[J] .Radiology, 2011, 258: 546-53.
RE: Long-term Outcomes of Cerebral Aneurysms in Children
TO THE EDITOR: I read with interest the article by Aymeric Amelot et al.1 (Long-term Outcomes of Cerebral Aneurysms in Children). They reported the long-term clinical (a mean follow-up of 8.3 years) and imaging outcomes of <15-year- old children treated for ruptured or symptomatic cerebral aneurysms and to identify prognostic factors for clinical outcome, recurrence, and rebleeding. they found that 68.6% children had a favorable outcome. As the article mentioned, studies based on 37 ruptured and 14 symptomatic aneurysms, and endovascular treatments (84%) or microsurgical procedures (16%) were performed. The series of this study and the number of cases of neurological worsening was so small that the statistical power was not sufficient enough to extract the true primary risk factor after multiple regression analyses, so the statistical analysis should be reviewed by a statistician. In addition, it is not recommended to analyze the clinical outcome of ruptured and unruptured aneurysms together because the comparability of the two different statues of aneurysms is relatively low, and many of them have reported their vast differences. In addition, there are many different factors affecting the prognosis of ruptured or unruptured aneurysms. For ruptured aneurysms, the most important factor affecting the prognosis of patients may be the clinical status of SAH at the time of onset (such as the Hunt Hess score, World Federation of Neurosurgical Societies (WFNS)) and the timing of treatment1-4. For unruptured aneurysms, the clinical prognosis is affected to some extent by surgery-related complications and recurrence of aneurysms. Therefore, in addition to the results already presented in the paper, we recommend separately discussing the clinical prognosis of ruptured and unruptured aneurysms and their influencing factors. Finally, the study retrospectively identified all pediatric cases of cerebral aneurysm from 2000 to 2015. It means that the research period has spanned 15 years of rapid development of endovascular treatment. Is the prognosis of aneurysms in children different after improvement of skills and strategy?5,6 So, we think it would be better to add relevant analysis and discussion to the article.
Reference
1. Mayberg M R , Batjer H H , Dacey R , et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association[J]. Stroke, 1994, 25(11):2315-2328.
2. Jaja Blessing N R,Saposnik Gustavo,Lingsma Hester F et al. Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study.[J] .BMJ, 2018, 360: j5745.
3. Goddard A J P,Raju P P J,Gholkar A,Does the method of treatment of acutely ruptured intracranial aneurysms influence the incidence and duration of cerebral vasospasm and clinical outcome?[J] .J. Neurol. Neurosurg. Psychiatry, 2004, 75: 868-72.
4. Zuo Qiao,Yang Pengfei,Lv Nan et al. Safety of coiling with stent placement for the treatment of ruptured wide-necked intracranial aneurysms: a contemporary cohort study in a high-volume center after improvement of skills and strategy.[J] .J. Neurosurg., 2018, undefined: 1-7.
5. Rubbert Christian,Patil Kaustubh R,Beseoglu Kerim et al. Prediction of outcome after aneurysmal subarachnoid haemorrhage using data from patient admission.[J] .Eur Radiol, 2018, 28: 4949-4958.
6. Pierot Laurent,Cognard Christophe,Anxionnat René et al. Remodeling technique for endovascular treatment of ruptured intracranial aneurysms had a higher rate of adequate postoperative occlusion than did conventional coil embolization with comparable safety.[J] .Radiology, 2011, 258: 546-53.