The NIHSS Bias: Why Right-Sided Middle Cerebral Artery Strokes Carry Higher Mortality and Complication Risks

Highlights

• Right-sided middle cerebral artery strokes (R-MCASs) are associated with a 19% higher odds of inpatient mortality compared to left-sided strokes (aOR, 1.19).
• Patients with R-MCAS face significantly higher risks of severe complications, including cerebral edema/herniation (aOR, 1.53) and hemorrhagic transformation (aOR, 1.25).
• Despite higher mortality, R-MCAS patients were less likely to receive intravenous thrombolysis but more likely to undergo endovascular thrombectomy.
• The findings suggest a systemic diagnostic bias in the National Institutes of Health Stroke Scale (NIHSS), which prioritizes language deficits over nondominant hemisphere symptoms like neglect.

Introduction: The Laterality Paradox in Stroke Care

The middle cerebral artery (MCA) is the most common site for acute ischemic stroke (AIS), representing a significant portion of the global burden of neurovascular disease. For decades, clinicians have utilized the National Institutes of Health Stroke Scale (NIHSS) as the gold standard for assessing stroke severity and determining eligibility for reperfusion therapies. However, a growing body of evidence suggests that the NIHSS may not be an equitable tool across all stroke types. Specifically, the scale is heavily weighted toward language and speech functions—abilities primarily localized to the left hemisphere in the vast majority of the population. Consequently, patients with right-sided middle cerebral artery strokes (R-MCASs), which often present with more subtle but equally devastating deficits such as hemispatial neglect and anosognosia, may receive lower NIHSS scores that do not accurately reflect the true extent of their neurological injury. This discrepancy raises a critical clinical question: Does the laterality of an MCA stroke independently influence inpatient outcomes and complications?

Study Design and Methodology

To investigate this phenomenon, researchers Albert et al. conducted a comprehensive retrospective cross-sectional analysis using data from the National Inpatient Sample (NIS) spanning from 2015 to 2022. The NIS is the largest publicly available all-payer inpatient care database in the United States, providing a robust, nationally representative sample for analysis.The study included adult patients (aged 18 years and older) primarily hospitalized for MCA strokes with documented NIHSS scores. The cohort was stratified into two groups: those with R-MCAS and those with left-sided MCA strokes (L-MCAS). The primary outcomes of interest were inpatient mortality, routine discharge (discharge to home), and various inpatient complications. Secondary outcomes included the receipt of reperfusion therapies, specifically intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT).To ensure the groups were comparable and to account for confounding variables such as age, comorbidities, and initial stroke severity, the researchers utilized propensity score-based inverse probability of treatment weighting (IPTW). Multivariable logistic regression was then employed to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results: A Striking Divergence in Clinical Outcomes

The analysis included a total of 489,360 acute ischemic stroke hospitalizations. Of these, 263,495 (53.8%) were categorized as L-MCAS, while 225,865 (46.2%) were R-MCAS. The findings revealed stark differences in the clinical trajectory of these patients based on the side of the brain affected.

Mortality and Discharge Disposition

Even after adjusting for confounding factors, patients with R-MCAS demonstrated significantly poorer outcomes. The odds of inpatient mortality were 19% higher for R-MCAS compared to L-MCAS (aOR, 1.19; 95% CI, 1.12–1.26; P<0.001). Furthermore, R-MCAS patients were significantly less likely to achieve a routine discharge to home (aOR, 0.786; 95% CI, 0.760–0.812; P<0.001), suggesting a higher need for long-term care or rehabilitation facilities.

Inpatient Complications

The study identified a heightened risk for several critical complications in the R-MCAS group:

• Cerebral Edema and Herniation: R-MCAS was associated with a 53% increase in the odds of developing cerebral edema or herniation (aOR, 1.53; 95% CI, 1.47–1.59; P<0.001).
• Hemorrhagic Transformation: The risk of bleeding within the infarcted area was 25% higher in the right-sided group (aOR, 1.25; 95% CI, 1.20–1.30; P<0.001).
• Sepsis: R-MCAS patients had a 35% increased likelihood of developing sepsis during their hospital stay (aOR, 1.35; 95% CI, 1.25–1.46; P<0.001).

Interestingly, L-MCAS was associated with a slightly higher likelihood of coma (aOR, 0.920 for R-MCAS compared to L-MCAS), which may be related to the profound impact of dominant hemisphere injury on global consciousness and communication.

Disparities in Reperfusion Therapy

The patterns of treatment also differed significantly by laterality. Patients with R-MCAS were significantly more likely to receive endovascular thrombectomy (aOR, 1.26; 95% CI, 1.22–1.30; P<0.001) but less likely to receive intravenous thrombolysis (aOR, 0.965; 95% CI, 0.937–0.994; P=0.018). This pattern suggests that R-MCAS patients may present later or with more severe large-vessel occlusions that are not captured early enough for IVT but eventually necessitate mechanical intervention.

Expert Commentary: The Nondominant Hemisphere Fallacy

The results of this study underscore a significant blind spot in current stroke assessment protocols. The NIHSS allocates up to 7 points for language and speech (aphasia and dysarthria), which are predominantly left-hemisphere functions. In contrast, only 2 points are allocated for neglect (extinction and inattention), a hallmark of right-hemisphere injury. Consequently, a patient with a massive right-sided stroke may have a lower NIHSS score than a patient with a smaller left-sided stroke that affects the Broca or Wernicke areas.

Biological and Clinical Plausibility

Why does R-MCAS lead to worse outcomes despite potentially lower initial scores? One mechanistic insight involves the concept of ‘clinical-radiological mismatch.’ Because right-sided deficits are more ‘silent’ or subtle—often involving spatial awareness rather than verbal output—patients and families may delay seeking care. This delay in presentation directly impacts the window for intravenous thrombolysis, explaining why R-MCAS patients received IVT less frequently.Furthermore, the higher rates of cerebral edema and herniation in R-MCAS suggest that by the time these patients are identified as having a severe stroke, the volumetric extent of the tissue at risk may be larger than in L-MCAS patients who present quickly due to obvious aphasia. The increased risk of sepsis may be secondary to more prolonged immobilization or higher rates of dysphagia and aspiration that go undetected in patients who cannot verbally communicate their distress but suffer from profound neglect.

Conclusion: Moving Beyond the Score

The findings from this large-scale analysis call for a re-evaluation of how we triage and assess acute ischemic stroke. Laterality is not merely an anatomical detail; it is a significant predictor of clinical outcome. The current NIHSS bias toward the dominant hemisphere may inadvertently lead to the undertreatment of right-sided strokes or a failure to anticipate the aggressive complication profile associated with them.Clinicians should maintain a high index of suspicion when evaluating patients with suspected nondominant hemisphere strokes. Recognition of subtle signs, such as mild neglect or anosognosia, must be prioritized. Future iterations of stroke scales may need to re-weight these symptoms to ensure that patients with R-MCAS are identified as high-risk early in their clinical course. Ultimately, achieving equity in stroke outcomes requires tools that accurately reflect the physiological impact of the injury, regardless of which side of the brain it strikes.

References

1. Albert S, Jain AK, Malhotra A, et al. Impact of Laterality on Inpatient Outcomes and Complications of Middle Cerebral Artery Acute Ischemic Stroke. Stroke. 2026. PMID: 41822970.2. National Institutes of Health. NIH Stroke Scale Training. 3. Powers WJ, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke. Stroke. 2019;50(12):e344-e418.