The importance of this study is the objective demonstration of time-dependent collateral recruitment and the correlation of collateral status with clinical outcome measures. A history of symptom fluctuation or progressive worsening since initial onset of stroke has traditionally been viewed as indicating that an at-risk area of brain is receiving diminished perfusion near the threshold for normal function.9
Despite conventional wisdom, no correlation could be demonstrated between a history of pre-hospital fluctuation or worsening and either the finding of diminished collaterals or as a predictor of greater risk for in-hospital worsening. Although the clinical history of pre-hospital symptom change was not predictive of clinical status, the extent of collaterals was. Despite the presence of a proximal MCA occlusion, the risk for in-hospital worsening for patients with adequate collaterals was not significantly greater compared with subjects who had no occlusions, regardless of whether an inclusive or strict definition was used for worsening. In contrast, the rate of worsening was nearly 4 times greater in subjects with proximal MCA occlusion but diminished collaterals.
Major clinical trials have used either change in NIHSS ≥ 1 or ≥ 4 to define worsening. In this study, the impact of collaterals was significant whether a broad definition of NIHSS ≥ 1 was used, or NIHSS ≥ 4 to target severe worsening. Whereas the occlusion patients with normal or increased collateral flow fared no worse than stroke patients with no visible occlusions, the fraction with diminished flow experienced a significantly greater risk of in-hospital progression of stroke deficits, to the point that patients with absent collaterals had a ten-fold increased risk of severe worsening or death. Diminished or absent collaterals, while only affecting only one-quarter of subjects with proximal MCA occlusion, was a clear harbinger of further worsening of stroke severity. Thus, the disparity in outcomes between case subjects and controls reported in is accounted for by the minority of cases with diminished collaterals.
Patients presenting with proximal MCA occlusions showed a time-dependent recruitment of flow to the symptomatic hemisphere through collateral vessels. Overall, half of such patients showed a symmetric extent of collaterals between hemispheres, and the remaining half was evenly divided between one subset that experienced augmented flow through collateral vessels (26%), and another with diminished flow in the same regions (26%). The fraction of patients with augmented flow remained constant. Although most patients appear to eventually achieve adequate collateral flow, the ability to generate augmented flow to the affected hemisphere appears to be established within the first hour. These findings suggest a possible intrinsic capacity for collateral flow that is important for clinical outcome.
This study contributes important advances in the current understanding of how collateral vessels influence outcome in acute stroke. First, data is presented to demonstrate an alteration in the extent of collaterals in the context of proximal arterial occlusion. Second, a time-dependent trend is identified implying a successful early (<1 hour) recruitment of collaterals in approximately three-fourths of stroke patients with proximal arterial occlusion, as well as a slow secondary recruitment phenomenon. Finally, CTA imaging can identify a unique subset of patients with diminished or absent collateral vessels in the symptomatic hemisphere. This group of patients experiences markedly higher risk for further worsening. Despite the abundance of emerging multimodal imaging techniques in the field of stroke, there is a paucity of data demonstrating a strong correlation between an imaging finding and clinical outcome.
There are inherent limitations involved with evaluating the role of collateral vessels. Ascertaining a history of fluctuation or progression relies on patient and family being capable of observing and correctly interpreting signs attributable to multiple domains of neurological function, which is fraught with limitations. Use of the NIHSS by properly trained staff is a more objective measure than report of pre-hospital symptoms. Use of CTA reveals the extent of patent arterial collaterals by observing contrast filling of vessel lumens, but cannot account for any difference in volume of flow within collateral vessels that may be induced by occlusion. Furthermore, the technique of identifying collaterals depends on an approximation based on vessels visualized in the sylvian fissure and leptomeningeal convexity region.
Prior studies have employed angiographic techniques to assess cerebral arterial collaterals in the context of acute to subacute ischemic stroke (see ). Tan et al10
compared the techniques used to visualize collateral vessels employed in earlier studies by Schramm3
and found that the less subjective ordinal scale used by Kim et al had higher interobserver agreement (κ = 0.669) and correlated significantly with infarct volume both in patients with persistent arterial occlusion and those who showed recanalization. Rosenthal et al12
employed a multivariable analysis model to study clinical and radiologic predictors of patient outcomes. More recently, arterial spin labeled MRA has been shown to accurately image collateral flow.13
Although other imaging techniques have successfully visualized leptomeningeal vessels in acute stroke, no correlation was found between abnormal visualization of leptomeningeal vessels and clinical status.14
This may have been due to small numbers of patients studied.
Angiographic Grading of Cerebral Collaterals in Prior Studies of Ischemic Stroke Patients
Given the predictive clinical implications of diminished or absent collateral vessels, CTA based assessment of collaterals may provide a clinically useful method of selecting patients likely to benefit from intra-arterial therapies. Further research correlating extent of collateral vessels, extent of perfusion defect-infarct core mismatch and clinical outcome may lead to advances in patient care. Other studies have found a relationship between perfusion parameters such as regional cerebral blood volume and cerebral blood flow and delayed contrast arrival on perfusion source images that suggests the role of collateral vessels.7
Future research to explore those relationships would be useful. Likewise, future research into treatments directed at improving cerebral blood flow, such as induced hypertension, may employ collateral vessel grading in their selection of patients. Some patients with diminished collateral vessels may not respond to such treatments despite being identified as a good candidate by perfusion mismatch, or they may prove to be the ideal candidates for such treatment due to their propensity for progression of deficits.