9.1.1 Clinical Presentation

A 76-year-old female patient presented to the emergency department 130 minutes after sudden onset of left arm and leg weakness with facial droop. Clinical examination confirmed a right middle cerebral artery (MCA) syndrome, National Institutes of Health Stroke Scale (NIHSS) 12.

9.1.2 Imaging Workup and Investigations

• 
  

  Noncontrast computed tomography (NCCT) performed shortly after presentation to the emergency department (145 minutes after symptom onset) reveals early infarction in the right insular, frontal, and temporal lobes, ASPECTS 6 (Fig. 9.1).

  
  
• 
  

  CT angiography (CTA) reveals occlusion of the right MCA-dominant M2 superior division (Fig. 9.1), and moderate collateral circulation.

  
  
• 
  

  CT perfusion (CTP) reveals increased mean transit time in the MCA cortical branch territories, with reduced cerebral blood volume (CBV) and cerebral blood flow (CBF) corresponding to the areas of early infarction on NCCT, but surrounding areas of normal CBV with mildly reduced CBF indicating tissue at risk of infarction, but potentially salvageable with reperfusion.

  

9.1.3 Diagnosis

Right M2 superior division occlusion with early infarction in the MCA territory. Abnormally perfused tissue surrounding the infarct (mismatch on CTP) indicating tissue at risk of infarction, but potentially salvageable with reperfusion.

9.1.4 Management

• 
  

  The patient had no contraindication to intravenous (IV) thrombolysis based on clinical history, clinical assessment, and CT findings.

  
  
• 
  

  She received an initial bolus and infusion of tissue plasminogen activator (tPA) commencing 190 minutes after the symptom onset. Endovascular therapy was considered appropriate based on time from onset of symptoms, location of the arterial occlusion, and CT findings suggesting potentially salvageable tissue. The time from symptom onset to groin puncture was 235 minutes.

9.1.5 Endovascular Treatment

9.1.6 Postprocedural Care

• 
  

  Transferred to the neurology high dependency unit for monitoring.

  
  
• 
  

  Six hours after the thrombectomy procedure, an emergent NCCT was performed due to a change in neurological status, revealing a small parenchymal hematoma within the infarcted territory and a moderate volume of subarachnoid hemorrhage/contrast staining (Fig. 9.2). A small area of new infarct was now discernible in periventricular white matter.

  
  
• 
  

  The patient was closely monitored with subsequent improvement in neurological status over 24 hours. Repeat NCCT 24 hours later showed no change in size of the hematoma, partial resolution of subarachnoid hemorrhage, and no further infarct extension.

  

9.1.7 Outcome

• 
  

  Right MCA infarct with hemorrhagic transformation.

  
  
• 
  

  Reperfusion therapy with IV-tPA and mechanical thrombectomy. Final infarct volume based on day 5 NCCT (Fig. 9.3) remained largely similar to the initial NCCT, and significantly smaller than the predicted infarct on CTP.

  
  
• 
  

  Discharged 5 days after admission to a rehabilitation hospital, with a modified Rankin score of 3.

  

9.1.8 Background

The Alberta Stroke Program Early CT Score (ASPECTS) is a standardized, quantitative, topographical scoring system for assessment of early ischemic changes in the MCA territory on CT. The early European Cooperative Acute Stroke Studies (ECASS) excluded patients with early ischemic changes on CT in greater than one-third of the MCA territory. ^{1 ,​ 2} The rationale for the exclusion was that early ischemic change in greater than one-third of the MCA territory was associated with severe stroke, poor outcome, higher frequency of spontaneous hemorrhagic transformation, and suggested proximal occlusion with poor collateral circulation, thus less likely to respond to thrombolytic therapy. ¹ This led to the “1/3 MCA rule”; early ischemic changes on CT in greater than one-third of the MCA territory is a recommended contraindication for IV-tPA therapy. However, assessing volume of infarcted territory on axial CT sections is difficult, and utilizing this technique to determine the presence of infarction in greater than one-third of the MCA territory is considered unreliable with poor interobserver variability. ^{3 ,​ 4 ,​ 5} To attempt to address these problems of the 1/3 MCA rule, the ASPECTS study group developed the ASPECTS scoring system to allow a simplified, standardized, alternative method of quantifying early ischemic changes on CT. ⁶ The initial ASPECTS study retrospectively reviewed imaging, clinical data, and outcomes of 203 consecutive patients treated with tPA at two stroke centers. Initial CT images were graded using ASPECTS and according to the 1/3 MCA rule. They found that for stroke neurologists, radiology trainees, and experienced neuroradiologists, the use of dichotomized ASPECTS (≤7 vs. >7) had better interobserver agreement than the 1/3 MCA rule. In addition, the dichotomized ASPECTS had better sensitivity and specificity than the 1/3 MCA rule for functional outcome. Baseline ASPECTS had an inverse correlation with NIHSS score and was a significant predictor of both functional outcome and symptomatic hemorrhage. ⁶

The ASPECTS scoring system divides the MCA territory into 10 discrete regions. Regions are weighed on a functional rather than a volume basis; thus, eloquent areas such as the internal capsule have the same weighing as larger volumes of MCA cortex. The MCA territory is divided into three subcortical and seven cortical regions. The subcortical regions are the caudate nucleus (C), lentiform nucleus (L), and internal capsule (IC). The cortical regions are the insular cortex (I); anterior, middle, and posterior MCA cortex at the level of the basal ganglia (M1–3); and anterior, middle, and posterior MCA cortex rostral to the basal ganglia (M4–6) ⁶ (Fig. 9.4). An ASPECTS is calculated by assessing each of the 10 regions, awarding 1 point for each normal region, and no point for a region that has early ischemic change, giving a total score out of 10. A score of 10 indicates a normal scan with no feature of early ischemia, and a score of 0 indicates ischemia throughout the MCA territory. Changes of early ischemia may be parenchymal hypoattenuation (abnormally reduced attenuation of a brain structure relative to other parts of the same structure or the contralateral hemisphere), loss of differentiation between gray and white matters, or focal swelling (sulcal or ventricular effacement due to compression by adjacent brain). At its inception, ASPECTS were calculated by assessing two 10-mm NCCT axial sections, one at and one just rostral to the level of the basal ganglia. ⁶ With increase in use of thinner sections on CT imaging, the ASPECTS scoring system has been modified to include all axial sections that include basal ganglia or supraganglionic structures, the boundary between these regions at the level of the caudate head.

9.1.9 Discussion

ASPECTS has value in prognosticating, and may assist with patient selection for acute stroke treatment. In the initial ASPECTS study, a baseline, pretreatment ASPECTS of 7 or less was strongly associated with an increase in the rates of death and functional dependency in patients treated with IV-tPA. ⁶ Subsequent larger studies confirm the strong correlation between pretreatment ASPECTS and probability of excellent functional outcome (modified Rankin score of 0–1) after treatment with IV-tPA, the Canadian Alteplase for Stroke Effectiveness Study demonstrating this effect in a relatively linear fashion. ⁷ Post hoc analysis of the pivotal National Institute of Neurological Disorders and Stroke (NINDS) tPA study found that higher ASPECTS (scores of 8–10) were associated with a greater extent of benefit from IV thrombolysis, a trend toward reduced mortality and smaller final infarct volumes. ⁸ Post hoc analysis of the ECASS-2 trial found an increased rate of thrombolysis-related parenchymal hematoma in patients with a pretreatment ASPECTS of ≤7. ⁹ Post hoc analysis of the Prourokinase Acute Cerebral Infarct Trial (PROACT-II), and review of the Interventional Management of Stroke (IMS-1) trial scans using ASPECTS, identified a clear treatment interaction when ASPECTS was used in a dichotomized fashion. In PROACT-II, patients with a pretreatment ASPECTS of >7 treated with intra-arterial (IA) prourokinase did better than controls, in contrast to those with a pretreatment ASPECTS of ≤7 who had no benefit. ¹⁰ In a review of IMS-1, patients treated with combined IV-IA therapy were compared with matched subjects from the NINDS ASPECTS analysis. Patients with a pretreatment ASPECTS of >7 were more likely to benefit from combined IV-IA therapy than from IV therapy alone. Patients with a pretreatment ASPECTS ≤7 were less likely to benefit from combined therapy and more likely to be harmed. ¹¹ The IMS-3 trial compared outcomes from acute stroke patients treated with IV-tPA therapy plus endovascular therapy with IV-tPA therapy alone. The trial failed to show benefit of endovascular therapy and was terminated early due to futility. ¹² One criticism of the trial and possible contributing factor for the lack of an outcome difference between therapies was recruitment of patients with low ASPECTS. Imaging criteria for exclusion in the trial included infarction in greater than one-third of the MCA territory on baseline CT. Supplementary methods state that “an ASPECTS of less than 4 could be used as a guideline when evaluating more than one-third region of territory involvement but was not considered a specific exclusion.” ¹² Post hoc analysis of IMS-3 ¹³ revealed that 92 patients had an ASPECTS of 0 to 4, and 186 patients had an ASPECTS of 5 to 7. After analysis, pretreatment ASPECTS was found to be a strong predictor of outcome—subjects with an ASPECTS of 8 to 10 were almost twice as likely to achieve a favorable outcome as those ≤7. Pretreatment ASPECTS was also a predictor of reperfusion with combined IV-IA therapy. However, the authors of the post hoc analysis concluded that there was insufficient evidence of a treatment by ASPECTS interaction. ¹³

In the case highlighted in this chapter, ASPECTS was only one of many clinical and imaging factors influencing the decision to treat and the chosen treatment methods. The patient had excellent baseline functional status, no significant medical comorbidities, evidence of potentially salvageable tissue on CTP, and a desire to undergo the available treatments. A baseline ASPECTS of 7 or less is not a contraindication for IV-tPA, and ASPECTS should not be used in isolation to prognosticate or select treatment. Notwithstanding, the potential for poorer outcome with lower ASPECTS may be useful to assist with patient selection for therapy.

A very low ASPECTS (0–3) implies a large area of early ischemic change in the MCA territory, and may be a predictor of malignant MCA infarction (Fig. 9.5, Fig. 9.6). ¹⁴ Patients with very low ASPECTS on presentation should undergo early repeat imaging to assess for potentially malignant MCA swelling, and aid in identifying patients who may benefit from surgical decompression. Determining infarct core size prior to acute reperfusion therapy is of increasing interest, as core size is a predictor of clinical outcome and response to therapy. In particular, patients with core volumes of more than 70 to 100 cc are more likely to have poor functional outcome regardless of reperfusion. ^{15 ,​ 16 ,​ 17} NCCT ASPECTS has a reasonable correlation with DWI MRI ASPECTS and thus for core infarct size, ^{18 ,​ 19} but remains inferior to CTP. ²⁰ The application of ASPECTS to CTA source data and perfusion maps has been investigated ^{20 ,​ 21 ,​ 22 ,​ 23 ,​ 24 ,​ 25} ; however, such applications are not widely utilized in a clinical setting.

There are limitations to the ASPECTS scoring system. ASPECTS can only attempt to quantify early ischemic change in the MCA territory, and thus has no value in infarction of other vascular territories. For example, a patient may have a disabling or potentially fatal stroke in the posterior circulation territory but will have a normal ASPECTS. Interobserver reliability of total ASPECTS is good but not excellent, although it is superior to that of the “1/3 MCA rule.” ^{6 ,​ 26 ,​ 27 ,​ 28} This is most likely secondary to the standardized and structured technique of ASPECTS. Given the potential for ASPECTS to prognosticate and modify patient selection for acute stroke therapy as discussed previously, the reliability of the score has been evaluated when used in a dichotomized fashion. The interobserver reliability falls to only moderate when ASPECTS is dichotomized at 7 (≤7 vs. >7), which may impact on its utility. ²⁹