Pathology of Intracranial Aneurysms in Children

Pathophysiology

Formation

• Unclear pathophysiology: Contemporary insight into the pathophysiology of intracranial aneurysms in general contradicts the classical concept of aneurysms being truly congenital lesions. Laboratory research (with specimens from adults) revealed an average age of collagen within aneurysms of less than 5 years, indicating a high turnover (72).
• Abnormal repair processes: An alternative hypothesis is the concept of an underlying vessel wall dysfunction with transient or permanent failure to repair insults. Abluminal and luminal factors are thought to play a role (73). In children, given the rarity of the risk factors associated with intracranial aneurysms in adults (including hypertension, advanced age, smoking, and drug abuse), it is likely that these faulty “defense” mechanisms explain the formation of aneurysms not associated with “offensive” factors such as head trauma, infection, or inflammation (74).

Etiology and classification

Although certain overlaps exist with regard to their etiology and configuration, pediatric aneurysms are most commonly classified into the following categories (49,74):

• Saccular (“berry”) aneurysms: Between 32% and 70% of pediatric intracranial aneurysms are of this type (see examples in Relationships to Other Disease States and Syndromes) (75). Given that hemodynamic factors may play only a limited role in the formation of pediatric aneurysms, their etiology is controversial (49).
• Nontraumatic dissecting aneurysms: These are four times more frequent in children than adults and often localize to the posterior circulation (see example in Evaluation of Intracranial Aneurysms in Children) (49). Their appearance is typically fusiform, resulting from intimal damage and the subsequent entry of blood into the subintimal space (74). These aneurysms may or may not present with subarachnoid hemorrhage, and focal arterial stenosis may contribute to an ischemic presentation (75).
• Giant aneurysms: A subset of dissecting aneurysms, giant aneurysms are also four times more frequent in children and form due to recurrent intramural hemorrhage (49). An “onionskin” appearance may be observed; these aneurysms most often present with mass effect rather than subarachnoid hemorrhage (74).

Giant, traumatic aneurysm in a 2-year-old child: (A) A 2-year-old child presented with daytime headaches, episodes of emesis, and overnight awakening several months after a car collision. At that time, both of the child’s parents required hospital evaluation for trauma. Outpatient MRI demonstrated a partially thrombosed giant right M1 dissecting aneurysm (yellow arrowheads). Coronal imaging (left) demonstrated a multilobulated configuration. (B) Sagittal pre-contrast (left) and post-contrast (right) T1-weighted images are shown. These images demonstrate variable contrast enhancement in the patent portion of the aneurysm (blue arrowhead) compared to the thrombosed component (yellow arrowheads). (C) AP view of right ICA angiography shows the patent portion of the aneurysm (yellow arrowhead) and its thrombosed component distorting perforators and branches with distal reconstitution of the M2 segments. (D) Long-term follow-up angiography revealed the bypass perfusion of the MCA territory (left) and retrograde filling of the M2 branches (right).

• Traumatic aneurysms: Representing 5% to 39% of pediatric aneurysms, traumatic aneurysms most often result from blunt head injury but can also be due to penetrating injury (49). These usually present 2 to 4 weeks after injury and result from the formation of a false lumen or pseudoaneurysm (74).
• Infectious (mycotic) aneurysms: These are caused by microbial infiltration of the vessel wall, which is subsequently weakened and prone to formation of a pseudoaneurysm (75). The most common causative organisms are Staphylococcus aureus, viridans streptococci, and various gram-negative bacteria (49,74). Fungal organisms are rarely encountered, although immunosuppression from treatment of hematologic malignancies may induce a particular susceptibility to the development of infectious aneurysms (49,74). The source of the infection may be septic emboli from bacterial endocarditis or contiguous spread from sinusitis, osteomyelitis, or cavernous sinus thrombophlebitis (74,75).

Fungal mycotic aneurysms in an immunosuppressed child: (A) This child with a history of B-cell acute lymphoblastic leukemia recently completed chemotherapy but developed a disseminated Fusarium infection with CNS involvement. The fungal infection and associated fungemia led to the formation of three cerebral mycotic aneurysms: two basilar artery aneurysms (white arrows) and one right superior cerebellar artery (SCA) aneurysm (yellow arrow), as revealed by DSA. (B) After growth was observed during short-interval follow-up imaging, a flow diverter was deployed in the basilar artery. MRA revealed decreased filling of the two basilar artery aneurysms and no changes to the SCA aneurysm. TOF MRA is susceptible to artifact due to the stent material; therefore, in-stent stenosis or thrombosis is not effectively evaluated by TOF MRA.

• Iatrogenic aneurysms: Another rare form of pediatric aneurysm, iatrogenic aneurysms occur after surgical intervention, such as brain tumor resection or radiotherapy (76,77).

Iatrogenic left cavernous ICA pseudoaneurysm: (A) This patient experienced injury to the left cavernous ICA during Le Fort I osteotomy, which led to the formation of a pseudoaneurysm. CT revealed persistent pseudoaneurysm (green arrow) filling immediately after the deployment of two flow-diverting stents (one flow diverter observed at yellow arrow). (B) 3-dimensional reconstruction created using rotational angiography demonstrated the telescoping configuration of the flow diverters in the left cavernous ICA. (C) Lateral and (D) 1-month follow-up AP views of DSA with left ICA injection revealed the position of the flow-diverting stents (slight narrowing in the left cavernous ICA; yellow arrows) with patency of the stents.

Location

In a literature review of 480 pediatric aneurysms, Beez et al. found the vascular distribution illustrated below (78). Whereas in adults the most common location for an aneurysm is the anterior communicating artery, the most common aneurysm site in children is the ICA, as determined by a review of 671 pediatric aneurysms of nontraumatic origin (42). Roughly half of these ICA aneurysms were located at the ICA bifurcation.

Vascular distribution of 480 pediatric aneurysms: The following abbreviations are used in the illustration: ACA, anterior cerebral artery; ACoA, anterior communicating artery; AICA, anterior inferior cerebellar artery; BA, basilar artery; ICA; MCA; PCA, posterior cerebral artery; PCoA, posterior communicating artery; SCA, superior cerebellar artery; VA, vertebral artery. Illustration from Beez et al (78).

Molecular/Genetic Pathology

• Predisposition: Genetic conditions predisposing for intracranial aneurysms in children are mainly sickle-cell anemia, phakomatoses (e.g., tuberous sclerosis complex and NF1), and heritable connective tissue disorders (e.g., Ehlers-Danlos and Marfan syndromes) (43,49,55,62,63).
• Manifestation: Important implications of underlying genetic pathology are higher rates of multiple aneurysms (60% of cases) and presentation at younger age (younger than 40 years), most evident for sickle-cell anemia (79,80). Heritable connective tissue disorders may affect the integrity of the arterial wall, thereby predisposing patients with these disorders to aneurysm formation and/or rupture (22).

Histopathology

• Abnormality of internal elastic membrane: Absence or irregular disruption of the internal elastic membrane is a common histopathological observation (78).