Low NIHSS... not so simple - Ep.1/4 - SLICE Worldwide 2023

LOW-NIHSS stroke：MT or medical treatment?

Acute large vessel occlusion (LVO) is a significant cause of acute ischemic stroke (AIS), with approximately 95.6% of lethal stroke cases and 61.6% of disabling stroke cases involving LVO1. In addition to causing fatal and disabling strokes, about 10% of AIS patients with LVO experience minor strokes. Without reperfusion therapy, up to 20% of these patients may experience a worsening of symptoms2-4. Research by Rajajee, V, et al. 5, found that among AIS patients with an NIHSS score of ≤5, approximately 18% had LVO, and this increased to 39% in those with scores between 0 and 86. Therefore, LVO can lead to strokes with both high and low NIHSS scores, including minor strokes.

Patients with minor strokes (NIHSS≤ 5) typically have favorable clinical outcomes7. However, those caused by LVO often experience a higher incidence of Early Neurologic Deterioration (END) and poor clinical prognosis5,8. Approximately 15% of these patients experience symptom instability on the first day and significant disability at 90 days9. If vascular recanalization is not achieved promptly, about one-third of these patients may not be able to walk independently at discharge10. The mechanisms for early neurological deterioration in LVO-induced minor strokes include poor collateral circulation, thrombus extension or secondary thromboembolism, and infarct expansion beyond the initial infarct area. Several observational studies and meta-analyses have been published on the safety and efficacy of Endovascular Therapy (EVT) in treating LVO-induced minor strokes, but the results vary.

In 2018, Sarraj, A, et al., compared EVT with medical treatment in a multicenter retrospective cohort study of LVO-induced minor strokes (NIHSS ≤5) from 2012 to 2017. The study included 214 patients (EVT treatment group 124, conservative treatment group 90), and found no significant difference between the two groups in the proportion of patients with a 90-day mRS ≤1 or ≤2 (55.7% vs 54.4%, P=0.47, and 63.3% vs 67.8%, P=0.77). Propensity-matched analysis yielded similar results, and the rate of symptomatic intracranial hemorrhage (sICH) was significantly higher in the EVT group (5.8% vs 0%; P=0.02). However, patients with M1 occlusion benefited more from EVT than from best medical treatment11.

In 2019, Manno, C, et al., retrospectively analyzed EVT and IVT (Intravenous Thrombolysis) for LVO-induced minor strokes (NIHSS ≤5) using data from the Swiss Stroke Registry. Out of 11,356 patients with acute strokes, 312 (2.7%) met the study criteria. After propensity score matching, each group had 108 patients. The study found no significant difference in the proportion of patients with a 90-day mRS ≤1 between the two treatment methods (63% vs 65.7%; OR 0.94, 95%CI 0.51–1.72; p = 0.840), and no difference in intracranial hemorrhage or 3-month comorbidity mortality rates. 12

In 2020, Goyal, N, et al., conducted a multicenter retrospective analysis comparing the safety and efficacy of EVT and medical treatment for LVO-induced minor strokes (NIHSS ≤5). The study included 251 patients (EVT group 138, medical treatment group 113), and found no significant difference between the groups in the proportion of patients with a 90-day mRS ≤1 or ≤2. EVT increased the occurrence of asymptomatic intracranial hemorrhage (4.6% vs 17.5%; P = .002).The authors noted that differences in baseline treatment between the two groups (lower NIHSS score at admission, higher proportion of proximal occlusion, and more use of thrombolytic drugs in the EVT group) may have influenced the results13.

In 2020, Saito, T, et al., reported data from the RESCUE Japan Registry 2, analyzing factors influencing favorable prognosis in LVO-induced minor strokes (NIHSS ≤5). The study included 272 patients, with 86 receiving thrombolytic treatment and 54 receiving EVT. 76.5% of all patients had a 90-day mRS ≤2. Multivariate analysis found that being under 75 years old ([OR], 2.42 [95%CI, 1.30–4.50], p=0.0052), having an NIHSS score of 0-3 at onset (OR, 3.08 [95%CI, 1.59–5.98], p=0.0009), receiving intravenous thrombolysis (OR, 2.86 [95% CI, 1.32–6.21], p=0.0077), and having a blood sugar ≤140mg/dL (OR, 2.37 [95% CI, 1.22–4.60], p=0.011) were independently associated with a good prognosis, while EVT was not (OR, 1.65 [95% CI, 0.71–3.88]).14

In 2022, Alexandre, A. M, et al., retrospectively analyzed data from 16 high-volume stroke centers, comparing the efficacy and safety of EVT and IVT for isolated M2 occlusion-induced minor strokes (NIHSS ≤5). The study included 388 patients, with 200 matched by propensity scores. The results found no significant difference in efficacy and safety between the timely EVT treatment group and the medical treatment + rescue EVT treatment group, suggesting that medical treatment first, with EVT as a rescue treatment, is a safe approach for M2 occlusion-induced minor strokes15.

In 2023, Schwarz, G, used propensity score matching analysis to retrospectively analyze the results of EVT and IVT treatment for LVO-induced minor strokes (NIHSS ≤5) from the International Stroke Thrombolysis/Thrombectomy Database. Each treatment method had 312 patients, and the study found that the proportion of patients with a 90-day mRS ≤1 or ≤2 was significantly lower in the EVT group compared to the IVT group (mRS ≤1: 57.5% vs 72.4%, p=0.001; mRS ≤2: 68.8% vs 78.9%, p=0.019), with more intracranial hemorrhage and subarachnoid hemorrhage occurring. The study suggests that EVT treatment is closely associated with poor prognosis16.

In 2023, Safouris, A and colleagues conducted a meta-analysis of 11 observational studies, including 2019 patients who received Endovascular Therapy (EVT) and 3171 patients who received medical treatment, all with NIHSS scores ≤5 and anterior circulation LVO. The analysis revealed no difference between the two groups in terms of 90-day modified Rankin Scale (mRS) scores of 0-1 and 0-2. However, the incidence of symptomatic hemorrhage was significantly higher in patients who underwent EVT compared to those who received medical treatment17.

Without aggressive treatment, approximately one-quarter to one-third of patients with LVO-induced minor strokes may experience neurological deterioration, leading to poor prognosis. Additionally, LVO is a high-risk factor for stroke recurrence, with about 33.3% of patients experiencing a recurrence within one year18. Therefore, active treatment, particularly vascular recanalization, is justified for LVO-induced minor strokes, both to reduce disability and to prevent stroke recurrence. However, there is still a lack of consensus on how to identify high-risk populations for these more aggressive treatments.

In 2019, the European Stroke Organisation's Minimally Invasive Neurotherapy Society made recommendations regarding the use of EVT for minor strokes caused by LVO19. These recommendations include:

1. EVT should be considered for patients with evident disabling strokes, such as significant motor function deficit, aphasia, or hemianopia.

2. EVT may be indicated even after intravenous thrombolysis if symptoms worsen.

3. There is no consensus among experts on the use of EVT for non-disabling strokes, such as unilateral sensory disturbances.

Additionally, other studies have identified high-risk factors associated with LVO-induced strokes. These include:

•           The condition of collateral circulation (robustness) 20-22. 

•           Occlusion location, including carotid artery occlusion and tandem occlusions23.

•           Time from onset to hospital arrival24.

•           Blood pressure variability25.

•           Uncontrolled blood glucose levels26.

•           Size of the infarct volume27.

A 2021 study by Seners, P, et al. 28, found that an increase of ≥4 points in the NIHSS within 24 hours of intravenous thrombolysis, indicating END, could predict poor outcomes following EVT in patients with LVO-induced minor strokes. They proposed an Early Neurological Deterioration of Presumed Ischemic Origin (ENDi) score, with a total of 4 points. In this scoring system, thrombus length ≥9mm scores 1 point, occlusion in the M2 segment scores 0 points, distal M1 scores 1 point, proximal M1, basilar artery, or tandem occlusions score 2 points, and internal carotid artery occlusion scores 3 points. The probability of ENDi with scores of 0, 1, 2, and 3-4 points is approximately 3%, 7%, 20%, and 35%, respectively.

In summary, there is currently a lack of high-sensitivity and high-specificity predictive markers, whether clinical or imaging-based, for identifying high-risk populations or determining who needs EVT for LVO-induced minor strokes. Although there is no consensus in the current research, with the advancement of vascular recanalization techniques and materials, the exploration of safe and effective endovascular recanalization treatments for patients with LVO-induced minor strokes is still necessary.

 Reference

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