There is insufficient evidence to support a strong recommendation about the diagnostic accuracy of imaging to detect pseudoaneurysms.

• In patients with pTBI and a high index of suspicion for cerebrovascular injuries, digital subtraction angiography (DSA) should be performed as soon as feasible to detect traumatic aneurysms, as rupture is associated with worse outcomes.

• Following pTBI, treatment of traumatic intracranial arterial aneurysms (TICA) detected by screening improves the likelihood of survival.
• As traumatic intracranial aneurysms may develop in a delayed fashion, vascular imaging should be repeated to improve outcomes by identifying such TICAs prior to rupture. There is insufficient evidence to indicate the optimal timing for either initial or repeat vascular imaging in order to rule out cerebral vascular injury.
• CTA has the ability to detect some TICA as compared with the gold standard, digital subtraction angiography (DSA), and should be used as an initial screening modality.

In the absence of direct scientific evidence, EXPERT CONSENSUS concluded that:

Timing

• For patients with pTBI, a CTA should be ordered to evaluate for vascular injury at the time of initial CT on presentation (100% consensus).
• In patients with pTBI, repeat vascular imaging should be obtained between 7-21 days post injury or prior to patient discharge from hospital (100% consensus).

CTA vs. DSA

• If there is a high clinical suspicion for vasoaspasm (VSP), DSA should be considered over CTA to enable urgent endovascular treatment. (92% consensus)
• DSA should be obtained in cases where vascular injury cannot be ruled out on CTA due to streak artifact from retained metallic fragments or where in-driven bone fragments or foreign bodies are adjacent to intracerebral vasculature (100% consensus).
• DSA should be performed in patients with CTA confirmed vascular injury (100% consensus).

Benefits, Harms, Accuracy

• The following characteristics are associated with higher risk of vascular injury, and should be considered when deciding about urgency and prioritization of vascular imaging (100% consensus:
  • wound trajectory through or adjacent to major brain vasculature
  • violation of multiple dural compartments
  • facio-orbito-pterional entry wounds
  • presence of intracerebral hematoma

No evidence or expert opinion supported distinct recommendations based on patient gender, age, wounding mechanism, or military vs. civilian context.

pTBI frequently results in cerebrovascular injuries, leading to conditions such as traumatic intracranial aneurysms (TICA), arteriovenous fistula (AVF), and cerebral vasospasm, which if untreated, can significantly increase morbidity and mortality risks.1,2 [BELL] The rupture of TICAs in particular could cause catastrophic intracranial hemorrhage, often resulting in death. Early detection is crucial for the management and planning of surgical or endovascular interventions, considering the size and location of the lesions. However, these lesions may not be immediately apparent post-injury, making delayed imaging crucial for accurate diagnosis. Despite the critical nature of early and accurate detection, there is a historical absence of high-quality, consensus-based guidelines recommending the optimal imaging modality and timing.

CTA offers a quick and accessible means for imaging the intracranial vasculature, yet DSA remains the more sensitive and specific gold standard, despite its lower availability and more invasive nature. The management of cerebrovascular injuries is complicated by the potential for delayed TICAs, which can develop subsequent to initial imaging.2,3 These pseudoaneurysms, disrupting all vessel wall layers and contained only by clot, pose severe risks upon rupture. Early and accurate diagnosis is key to enabling effective endovascular and surgical treatments, underscoring the importance of repeated imaging with appropriate timing to improve patient outcomes.

The current guidelines effort endeavored to address the evidence related to optimal diagnosis and treatment of vascular injury from penetrating trauma. This section focuses on the evidence related to diagnosis, addressing three key areas: 1) the accuracy of DSA and CTA in pTBI, 2) the benefits and harms of DSA, and 3) the optimal timing of initial and delayed vascular imaging.

The prior penetrating head injury guidelines addressed the "Neuroimaging in the Management of Penetrating Brain Injury" and the "Vascular Complications of Penetrating Brain Injury."4,5. Concerning Neuroimaging, a total of 24 articles were included as direct evidence to support recommendations made at the level of option. Only two of the 24 articles [AARABI 1994; BENZEL 1991] addressed the utility of diagnostic cerebral angiography in the setting of pTBI.3,6 The remaining 22 articles cited as direct evidence addressed the utility of CT and plain skull xrays in pTBI. The routine performance of CTA was not addressed in this chapter. These two papers supported the recommendation, at the level of Option (Level III/IV), that a cerebral angiogram should be performed in patients where vascular injury is suspected, including those with wound trajectories near the Sylvian fissure, supraclinoid carotid carotid, and cavernous or other venous sinuses. Unexplained or delayed subarachnoid hemorrhage or other hematoma should also prompt the performance of catheter DSA.

Accuracy of CTA and DSA

Three studies (N=174) found the sensitivity of CTA, with DSA as the reference standard, to be 36%, 50%, and 73% for cerebral artery injury in a civilian setting in the United States with most patients victims of GSWs (86%, 86%, and 89%, Table 1).7-9 [ARES, BODANAPALLY, MEYER] One study (N=45) reported lower sensitivity with CTA when metal artifacts were present (67%). [BODANAPALLY] This study also reported a range of sensitivities across three different readers (64% to 73%, no metal artifacts). Specificity was 85%, 88%, and 94% across the same three studies, with no change associated with metal artifacts. The range of specificities across three readers in one study was 84% to 100%.20 Positive predictive value (PPV) of CTA for arterial injury was 50%, 67%, and 89% and ranged from 74% to 100% across three readers; NPV was 62%, 83%, and 88% and ranged from 77% to 85% across three readers. [ARES, BODANAPALLY, MEYER] In one study, the number of DSAs needed to identify one patient with a treatment-requiring lesion not found on CTA was 5.6. [MEYER]

Diagnostic accuracy of CTA varied across studies (especially sensitivity), across readers within one study, and whether or not metallic artifacts were present. These studies provide moderate strength evidence that DSA detects a greater number of vascular injuries than CTA in the setting of GSW to the head. These studies also provide very low strength of evidence that diagnostic accuracy of CTA to detect pseudoaneurysms is moderate to high when using DSA as the reference standard. However, due to other factors such as severity of injury and risk of neurological complications, the evidence is insufficient to determine when DSA should best occur or when DSA may be preferred over CTA.

Benefits and Harms of DSA

Ten studies meeting inclusion criteria for formal use as evidence reported results of cerebral angiography in patients with pTBI, with a total of more than 1320 angiograms conducted (number not reported in one study) (Table).2,8-16 Eight studies were case series, and did not compare angiography to another method of diagnosis (though one of these reported autopsy results in patients who died);16 two studies,8,9 also described in Key Question 2, compared cerebral angiography with computed tomography (CT) angiography. Three studies were conducted in the United States, three in South Africa, and four in Middle Eastern countries; populations were military in three studies, civilian in five, and mixed in two. Most patients were young men (average proportion male 90% and average mean age 25.5 years across studies), and the range of the average baseline GCS scores was 8.3 to 11 across five studies that reported this severity measure. Several other studies were excluded that reported very few angiograms and/or vascular lesions or had unclear reporting of clinical outcomes.7,17-21

Benefits. The primary benefit from screening for traumatic intracranial arterial aneurysms (TICAs) and cerebral vasospasm (VSP) is the potential for lifesaving/morbidity-reducing intervention(s) that would not have occurred without screening. The rate at which TICAs were identified varied across seven studies,2,8-13,15 from 3.6% in a military population in Iran (8 TICAs in 223 angiograms) to 40% in an Israeli study of civilian and military patients (10 TICAs in 25 angiograms); the weighted average across studies was 8.6%. When identified, TICAs were usually treated (55% to 100% of patients with TICAs treated in 7 studies2,10-15); some untreated patients recovered spontaneously, some refused treatment, and some died. Between 55% and 100% of patients with angiography identified TICAs (with or without other cerebrovascular abnormalities) underwent surgery or endovascular intervention and survived (5 studies,10-13,15 weighted average 65% treated). These studies provide low strength evidence that interventions to treat TICA found during screening improve the likelihood of survival.

Five studies reported Glasgow Outcome Scale (GOS) scores for patients with TICAs, on a scale from 1 to 5 with higher scores representing better outcomes. Mean GOS ranged from 3.1 to 4.4 (severe to moderate disability) across three studies; in the fourth, 66% had scores of 4 or 5 (moderate to low disability). In the fifth most recent study, mean GOS ranged from 1-5 with a mean of 4.9 Three studies also reported VSP,2,13,16 with rates between 2.7% and 54% of angiograms; the study with a rate of 54%2 reported treating all identified lesions, but did not describe treatment outcomes. The other four studies did not report treatment for VSP.

Harms. The primary harms of screening for TICA and VSP are any increase in morbidity/mortality due to the screening process (cerebral angiography), as well as any increase in morbidity/mortality due to any intervention provided because of a positive screen. The data on harms of screening and harms of treatment due to screening are sparse. One study stated there was "no procedure-related morbidity or mortality" and no groin complications.12

Diagnostic Accuracy. Two studies reported information relevant to the diagnostic accuracy of cerebral angiogram. Because cerebral angiogram is most often considered the reference standard for detection of intracerebral vascular lesions, we did not identify studies reporting true diagnostic accuracy outcomes for angiography, and we did not assess strength of evidence for these outcomes. One study described a U.S. civilian population, with 45 patients who received both cerebral angiography and CTA.8 Several reviewers assessed CTA results retrospectively, with a final reading adjudicated by a fourth reviewer. The adjudicated CTA result identified the same seven TICAs as the cerebral angiogram. However, the initial clinical CTA reading identified five TICAs versus seven seen on cerebral angiography.

A study from South Africa found one patient with a TICA among 15 undergoing cerebral angiography.16 The same lesion was found at autopsy in this patient; in addition, an autopsy found a ruptured TICA in another patient 11 days after injury, in whom an angiogram on admission had been normal. It is unclear whether the initial angiogram missed an aneurysm present then, or whether the TICA developed during the 11-day interval between admission and death.

One study from Turkey did not meet inclusion criteria (62% with intracranial injury [and some of those injuries may not have been penetrating] which is less than the inclusion cutoff of 85% with penetrating injury when study finding are not reported by penetrating versus nonpenetrating injury), but reported 115 patients with missile head injuries who received conventional angiography; 82 patients had magnetic resonance angiography (MRA) as well as angiogram.22 Cerebral angiography identified traumatic pseudoaneurysms in 21 patients, of which MRA detected three and missed 18; angiography identified 23 patients with vasospasm, of which MRA detected five. It was unclear whether every patient with TICA or VSP identified on angiogram also had an MRA; however, authors concluded that digital subtraction angiography (DSA) was preferable to evaluate these lesions.

Another study that did not meet inclusion criteria (75% with penetrating brain injury) retrospectively reviewed the charts of patients from the Iraq war and reported that 47% of 57 patients were found to have VSP (mean duration 14.3 days) identified by CTA.1 Most of these injuries were blast-related (82%). This study found that intracranial vasospasm was associated with TICA (48% of patients had both a TICA and vasospasm, p=0.05) and mortality (15% of patients with vasospasm died vs. 0% without vasospasm, p=0.029), as well as hemorrhage (p=0.03) and number of lobes injured (p=.0012). Discharge GOS was worse in patients with vasospasm (2.78 vs. 3.68, p=0.002). Ten patients (37%) were treated with medical management including hypertensive, hypervolemic, and hemodilution therapy as needed; 17 patients (63%) also received endovascular interventions including micro-balloon angioplasty. GCS scores improved with medical management alone and with medical management plus endovascular therapy. There is insufficient evidence to determine the diagnostic accuracy or harms of cerebral angiography and low strength evidence that screening for TICA with cerebral angiography improves the likelihood of survival.

Timing of Initial and Repeat Vascular Imaging

One study (N=181) in South Africa in victims of stab wounds to the head reported outcomes in patients who underwent angiography within 7 days of injury or after 7 days and reported no statistically significant difference in the identification of vascular injury (p=0.183) between early and late angiography, although a higher proportion of patients were found with vascular injury in the group (N=51) who underwent angiography after 7 days (41% vs. 31%).13[DUTREVOU] This study provides very low strength evidence of no difference between early and late angiography. Of the 21 patients with TICA, there was one death in the group who underwent late angiography (1/6 [17%] vs. 0/15 [0%]). However, due to the small number of patients with TICA and very few deaths, it is not possible to determine if angiography before or after 7 days of injury is preferred, although the study authors concluded that angiography should occur as soon after admission as possible.

Nine case series were included which addressed benefits and harms of screening for delayed vascular complications and included both military and civilian populations. Most injuries were blast-related or GSWs. The three largest case series included 26 patients with pTBI and 60% blast-related intracranial vascular injury in Iraq,2 [BELL] 13 U.S. patients with GSWs,23 [DAWOUD] and 24 mostly civilian patients in Israel12 [COHEN] and are discussed below. The time to second vascular imaging varied across the nine studies. All studies were rated high risk of bias due to study design.

In one case series (N=26), all patients received DSA and repeat angiography.2 [BELL] Of those 26 patients, four experiences a TICA rupture, one each on days 6, 14, 23, and 32. Additionally, most intracranial vessels that were not treated (9/10) experienced resolution of their vascular injury. When including patients with intracranial vascular injury or extracranial vascular injury, the mean time to aneurysm interval expansion was 24 days (range 8 to 75 days).

A second case series (N=13 patients with GSWs and follow-up CTA) reported 44.4% vascular injury on initial CTA.23 [DAWOUD] Mean time to repeat CTA was 6.8 days. Of those 13 patients, seven had no vascular injury on initial CTA and six of those patients had no vascular injury on follow-up. However, one patient had a TICA on repeat CTA. Of the six patients with vascular injury on initial CTA, four had similar findings on follow-up CTA. However, two patients had new findings on repeat CTA (VSP of anterior cerebral artery and posterior cerebral artery and thrombus of superior sagittal sinus). Additionally, two patients with vascular injury on initial CTA had a negative follow-up CTA. Three patients had follow-up angiograms (1 with no vascular injury and 2 with vascular injury on initial CTA) and follow-up imaging had similar findings.

A third case series (N=24 with repeat imaging; details provided for 9 TICA patients).12 Of nine patients with TICA on initial angiogram, all were successfully treated; [COHEN] it is presumed that follow-up vascular imaging with angiography or CTA demonstrated resolution or improvement. Of 15 patients with no TICA on screening angiography, no new TICAs were detected on repeat imaging.

These studies plus the smaller case series in the table provide low strength evidence that repeat vascular imaging may yield different findings from initial imaging (e.g., new or unrecognized vascular injury, worsening injury, improved injury [with or without treatment], resolution of vascular injury).11,14,24-26 [AMIRJAMSHIDI -1996, HADDAD, OZKAN, ROSTOMILY, SWEENEY?, YOON] There is insufficient evidence to determine the best interval between initial and follow-up vascular imaging, with most studies reporting a repeat imaging interval between 1 and 5 weeks, although longer intervals are also reported.

Evidence for CTA vs. DSA to detect cerebrovascular injury from pTBI

The importance of timely and accurate diagnosis of traumatic pseudoaneurysms following penetrating traumatic brain injury (pTBI) is significant, given their high risk of growth and rupture leading to high mortality. The discussion around the best screening modality for detecting cerebrovascular injuries post-pTBI highlights the complexity and urgency of this medical challenge. Traumatic pseudoaneurysms represent the most common histologic type observed after pTBI, necessitating urgent management to prevent life-threatening consequences. The treatment of pTBI induced traumatic cerebrovascular injury will be addressed in Sections VII-6, VII-7, and the Management Algorithm. This section addressed issues related to imaging of cerebrovascular imaging specifically.

Historically, the guidelines for managing penetrating brain injuries have recommended vascular injury screening using angiography, particularly in cases where the trajectory of the wound suggests an increased risk of vascular injury.4,5 However, advancements in diagnostic imaging and a lack of consensus in the literature have led to a debate over the optimal screening regimen, timing of imaging, and specifically between CTA and DSA.

The scientific foundation, one prospective study and two retrospective study led to a level II recommendation in support of DSA for high-risk patients.7-9 However, the data reported in the prospective study were insufficient to calculate sensitivity and specificity of CTA to detect pseudoaneurysms due to the possibility of one individual having multiple pseudoaneurysms and other methodological concerns limited the impact of the study. The retrospective studies evaluated the diagnostic accuracy of CTA against DSA and showed high sensitivity, specificity, and predictive values for detecting pseudoaneurysms when both modalities were in agreement. Yet, the initial interpretation of CTA results missed a significant proportion of traumatic intracranial arterial aneurysms, and missing data for a third of the CTA-DSA pairings reduces confidence in these results. This highlights the potential limitations of relying solely on CTA for initial diagnosis without considering DSA for confirmation, especially in ambiguous cases.

While both CTA and DSA offer valuable insights into cerebrovascular injuries post-pTBI, the decision on which modality to employ should be guided by the specific clinical context, including the availability of technology, expertise, and the patient's condition. Given the high stakes of missing or delaying the diagnosis of a traumatic pseudoaneurysm, a conservative approach involving the use of the most accurate and reliable diagnostic tools available is warranted. Screening for traumatic pseudoaneurysms should be conducted as soon as feasible, with a preference for DSA where practical, given its role as a reference gold standard. However, in settings where DSA is not readily available or feasible, CTA serves as a critical tool, with the understanding that follow-up or confirmatory testing may be necessary. The ultimate goal is to ensure the prompt and accurate detection of these potentially life-threatening injuries to facilitate timely and appropriate management.

Benefits and Harms of DSA

The discussion of the diagnostic accuracy of DSA and CTA above underlines the importance of accurate screening and detection. It can be argued that the most significant harm of DSA is in not performing one. Missing a traumatic aneurysm that subsequently ruptures is a worst case scenario, and in skilled hands entirely preventable. In context, the prior penetrating head injury guidelines provided recommendations at the lowest level for that work, or Option (Level III/IV), which admixed low level evidence with expert opinion. The currently available evidence (Level III) related to this question supports screening for traumatic intracranial aneurysms with DSA to improve survival. Coupled with the Level II recommendation supporting DSA over CTA in high-risk patients with pTBI, this subject represents one of the most meaningful areas of this guidelines.

Because DSA is considered the reference standard for cerebrovascular imaging, it is possible to assess the diagnostic accuracy of CTA in comparison (see above). There currently is no reference standard for DSA, and therefore no evidence backing its gold-standard designation.

Timing of Vascular Imaging

The question of when to perform vascular imaging following a penetrating brain injury is one that is incompletely addressed by current high quality, includable evidence. That said, there may be none more important. The incidence and natural history of traumatic aneurysms from pTBI has been studied and is, at least in part, known.2,3,10,14 We know that TICA's can form immediately or in a delayed fashion following pTBI. We know that TICA's can grow over time and rupture if not treated. The discomfort associated with the idea that some TICA's can heal or resolve without treatment is palpable, and yet does not diminish this possible outcome in limited circumstances. We now can say, based on evidence that resulted in a level III recommendation, that because traumatic aneurysms do change or perhaps develop in a delayed fashion, repeat vascular imaging should be obtained. The question concerning exactly when to perform the first imaging study and when to perform repeat imaging will be addressed by expert consensus in the absence of direct evidence.

A key impetus for updating the pTBI guidelines was diverse views in the field related to screening for and treating TICAs. Here we provide evidence-based and consensus recommendations aimed at identifying and promoting best care practices. In response to gaps in direct scientific evidence that include the optimal timing for initial and repeat vascular imaging and specific clinical indicators for penetrating traumatic brain injury (pTBI), an expert consensus through Delphi voting (Level C) offers guidance on the utilization of Digital Subtraction Angiography (DSA) and Computed Tomography Angiogram (CTA) in specific scenarios. The consensus underscores the importance of precise diagnostic approaches in managing pTBI, reflecting unanimous agreement (100% consensus) on several key recommendations including the high risk pTBI features that should prompt DSA. These include injuries with a wound trajectory that intersects or lies adjacent to major cerebral vasculature, violations involving multiple dural compartments, facio-orbito-pterional entry wounds, or the presence of an intracerebral hematoma. In situations where CTA is unable to conclusively rule out vascular injury (nearly all cases) - often due to interference from streak artifacts caused by retained metallic fragments or bone fragments/foreign bodies near intracerebral vasculature - DSA is recommended to ensure accurate diagnosis. For patients whose CTA results have confirmed vascular injuries, obtaining a DSA is advised to further investigate and plan appropriate interventions. Our panelists feel that DSA has numerous important advantages over CTA including improve sensitivity and specificity along with the ability to treat identified pathology. We acknowledge that it does have procedural risks which CTA does not.

Upon the initial CT scan for patients with pTBI, a CTA should be conducted to screen for any vascular injuries, providing a comprehensive understanding of the extent of damage from the outset. It is suggested that repeat early vascular imaging be performed between 7 to 21 days following the injury or before the patient's discharge from the hospital. This recommendation aims to identify any delayed vascular complications - in particular TICA - that are known to arise in delayed fashion.

An additional recommendation concerning vasospasm associated with pTBI was also made. Direct evidence meeting inclusion criteria concerning vasospasm was lacking. Referencing the section on treatment (Section VII-6, Treatment of Traumatic Pseudoaneurysms), the clinical significance of pTBI induced vasospasm remains somewhat uncertain.1 The clinical associations outlined above were enough to formulate a recommendation that, should vasospasm be suspected, a diagnostic cerebral angiogram should be performed to facilitate intervention should the clinician choose to do so (92%).

These expert consensus recommendations highlight a strategic approach to diagnosing and managing vascular injuries in pTBI, emphasizing the critical role of DSA and CTA in ensuring timely and effective care.

It is imperative to conduct further research comparing Computed Tomography Angiogram (CTA) and Digital Subtraction Angiography (DSA) in patients with penetrating traumatic brain injury (pTBI) to discern their relative efficacies, sensitivities, and specificities. As advancements in CTA technology continue to enhance its diagnostic accuracy, it's conceivable that DSA's role might diminish due to its invasive nature and associated higher morbidity risks. Moreover, in-depth investigations into the progression of vascular lesions post-pTBI are crucial for establishing the most opportune time for diagnostic imaging. These studies will not only refine our understanding of lesion development but also aid in refining the most effective timing for imaging, thereby optimizing patient outcomes. Other studies should focus on the development and validation of advanced imaging modalities or techniques that surpass the current limitations of CTA and DSA, particularly in sensitivity, specificity, and the ability to minimize artifacts from metallic fragments. Research into machine learning algorithms that can improve image interpretation and reduce variability among readers could also be transformative. There is also a significant gap in understanding the optimal timing for initial and repeat imaging to detect vascular injuries post-pTBI. Longitudinal studies that track the progression of vascular injuries over time could provide invaluable insights into when these injuries manifest and evolve, potentially leading to more timely interventions. The development of biomarkers for vascular injury that could predict the development of TICA or AVF after pTBI would be powerful. Such biomarkers could facilitate earlier identification of patients at high risk of developing these vascular complications, guiding more targeted imaging and intervention strategies.