Stroke is a major cause of mortality and persistent neurological disability worldwide.[1] The contemporary definition of stroke emphasizes an acute neurological dysfunction attributable to focal injury of the central nervous system from a vascular cause.[2] Ischemic stroke represents a substantial proportion of cerebrovascular events and develops when cerebral blood supply is interrupted, resulting in tissue hypoxia, metabolic failure, and neuronal injury.

The extent of neurological impairment after acute ischemic stroke depends on multiple interacting processes. Following cerebral ischemia, reduced oxygen and glucose availability causes depletion of cellular energy reserves, loss of ionic homeostasis, excitotoxicity, calcium influx, mitochondrial dysfunction, oxidative stress, and activation of inflammatory pathways. Inflammation has therefore emerged as an important contributor to both the pathogenesis and clinical evolution of ischemic stroke.[3]

Accurate assessment of neurological severity is important for prognostication and clinical decision-making. The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological assessment instrument used to quantify deficits associated with stroke. Higher NIHSS scores generally indicate greater neurological impairment.

Although clinical assessment and neuroimaging remain fundamental, biochemical biomarkers may provide supplementary information regarding the biological severity of cerebral injury. Two biomarkers of particular interest are C-reactive protein (CRP) and serum ferritin.

CRP is an acute-phase protein predominantly produced by hepatocytes in response to inflammatory stimulation. Elevated CRP reflects systemic inflammatory activation and has been associated with cardiovascular and cerebrovascular disorders. Previous research has demonstrated associations between elevated CRP and stroke severity, poor functional outcomes, and mortality.[4,5] Bian et al. reported that elevated CRP during the early phase of acute ischemic stroke was associated with poor functional outcome.[4]

Ferritin is primarily an intracellular iron-storage protein but also functions as an acute-phase reactant. Iron has been implicated in ischemic neuronal injury through oxidative mechanisms. Reperfusion can promote free-radical production, while iron may facilitate oxidative reactions that contribute to additional cellular damage. Elevated serum ferritin at admission has consequently been investigated as a marker of greater stroke severity and adverse prognosis.[6,7]

Study design and setting A hospital-based cross-sectional study was conducted in the Department of General Medicine at McGann District Hospital, Shivamogga. The study was conducted over one year, from June 2023 to June 2024. The minimum calculated sample size was 115 patients. Study participants A total of 115 symptomatic patients with acute ischemic stroke were included. Patients fulfilling the eligibility criteria and providing informed written consent were enrolled. Inclusion criteria Adult patients admitted with symptomatic acute ischemic stroke during the study period who consented to participate were eligible. Exclusion criteria The study excluded patients: • younger than 18 years; • who were pregnant or lactating; • with hemorrhagic stroke; • with inflammatory or neoplastic conditions capable of elevating CRP and serum ferritin; and • with anemia, defined as hemoglobin <13 g/dL in males and <12 g/dL in females. These criteria were specified in the original thesis methodology. Clinical assessment Demographic information was collected using a semi-structured questionnaire. Detailed medical history and neurological examination were recorded using a standardized proforma. Relevant vascular risk factors, including hypertension, diabetes mellitus, ischemic heart disease, smoking, and alcohol consumption, were documented. Laboratory investigations included complete blood count, renal function tests, liver function tests, fasting lipid profile, random blood glucose, CRP and serum ferritin. Electrocardiography and two-dimensional echocardiography were performed. Neuroimaging included non-contrast CT of the brain, while MRI with MRA and carotid artery Doppler were undertaken when required. Biomarker measurements Venous blood samples were collected from each participant at admission. CRP was measured using an instrument based on the principle of turbidimetry. Serum ferritin was measured using a Beckman Coulter Chemistry Analyzer based on spectrophotometry. Assessment of stroke severity Stroke severity was evaluated at discharge using the NIHSS. According to the categorization employed in the thesis: NIHSS score Stroke severity 1–4 Minor 5–15 Moderate 16–20 Moderate-to-severe 21–42 Severe The discharge NIHSS results were subsequently compared and correlated with admission CRP and serum ferritin concentrations. Statistical analysis Data were entered into Microsoft Excel and analyzed using SPSS version 26. The thesis reports calculation of percentages and proportions and use of inferential statistical testing. Correlation coefficients reported in the thesis were used to describe relationships between NIHSS and the two biomarkers. Statistical significance was considered at p<0.05. Ethical considerations The study was conducted after Institutional Ethics Committee approval. Written informed consent was obtained from study participants.

A total of 115 patients with acute ischemic stroke were evaluated.

Table 1. Demographic characteristics of study participants

Mean age: 49.39 ± 14.10 years

Patients aged >60 years constituted the largest age group (27.83%), followed closely by those aged 51–60 years (26.96%). Males constituted nearly two-thirds of the study population.

Table 2. Risk factors among acute ischemic stroke patients

Hypertension was the most frequently documented risk factor (45.22%), followed by smoking (34.78%) and diabetes mellitus (29.57%).

Table 3. Distribution according to NIHSS severity at discharge

The majority of participants (67.83%) had moderate stroke at discharge. Moderate-to-severe stroke occurred in 21.74%, while mild and severe categories each represented 5.22%.

Table 4. Admission CRP according to NIHSS severity

CRP increased progressively across NIHSS categories. Patients with severe stroke had the highest mean CRP concentration, whereas those with minor stroke had the lowest. The difference across severity groups was statistically significant (p<0.0001).

Table 5. Admission serum ferritin according to NIHSS severity

Serum ferritin demonstrated a similar progressive relationship. Mean ferritin increased from 163.20 ± 117.36 ng/mL among patients with minor stroke to 416.39 ± 90.33 ng/mL in severe stroke.

Table 6. Correlation of NIHSS with CRP and serum ferritin

Both biomarkers demonstrated strong positive correlations with NIHSS. The thesis reported a slightly greater correlation coefficient for CRP (r=0.99) than for serum ferritin (r=0.97). Both correlations were statistically significant.

Importantly, these results demonstrate association rather than independent predictive superiority. The thesis does not provide a formal statistical comparison between the two correlation coefficients, ROC analysis, adjusted regression, sensitivity/specificity, or optimal biomarker cut-offs; therefore, CRP should not be described as statistically superior to ferritin on the basis of these data alone.

The present study demonstrated significant relationships between two readily measurable biochemical markers—CRP and serum ferritin—and neurological severity among patients with acute ischemic stroke. Both biomarkers increased progressively across NIHSS categories, and both demonstrated strong positive correlations with NIHSS. The mean CRP concentration increased from 42.30 ± 14.06 in minor stroke to 351.77 ± 97.83 in severe stroke, with a statistically significant difference across NIHSS categories (p<0.0001). Similarly, mean ferritin increased from 163.20 ± 117.36 ng/mL in minor stroke to 416.39 ± 90.33 ng/mL in severe stroke (p<0.0001). These observations are biologically plausible because both systemic inflammation and oxidative stress contribute to ischemic neuronal injury. CRP is an established acute-phase reactant reflecting inflammatory activation. In acute cerebral ischemia, inflammatory signaling occurs in response to tissue injury, and higher CRP concentrations may consequently accompany more extensive neurological damage. Bian et al. evaluated CRP as a predictor of outcome in acute ischemic stroke and demonstrated that increased CRP during the first 24 hours was significantly associated with poor functional outcomes.[4] Den Hertog et al. similarly reported that CRP in the very early phase of acute ischemic stroke was associated with poor outcome and death.[5] Shoaeb et al. reported a positive correlation between serum CRP and NIHSS (r=0.54, p=0.006). Patients with severe ischemic stroke demonstrated significantly greater CRP concentrations than patients with mild-to-moderate stroke.[8] The thesis specifically notes that these observations support its own finding that increasing stroke severity was accompanied by increasing CRP. Ferritin provides a different but potentially complementary biological perspective. In addition to reflecting iron storage, ferritin behaves as an acute-phase reactant. Iron can contribute to oxidative tissue injury following cerebral ischemia and reperfusion. Excessive iron availability may facilitate generation of reactive oxygen species and exacerbate neuronal damage.[6] Garg et al. observed a significant positive association between serum ferritin and acute ischemic stroke severity (p<0.001) and found that higher admission ferritin was associated with clinical deterioration and poorer outcomes.[7] The thesis also cites Amalia and Wahyuni, who reported significant positive correlations between serum ferritin and NIHSS at admission and on day seven. The magnitude of the correlations in the present dataset was substantial: r=0.99 for CRP and r=0.97 for ferritin. These findings suggest that increasing neurological impairment was accompanied by increasing concentrations of both biomarkers. Nevertheless, the results require cautious interpretation. Because the correlation coefficients are reported from the thesis without multivariable adjustment, they do not establish that either biomarker independently predicts stroke severity. Furthermore, although the numerical correlation for CRP was marginally higher than that for ferritin, no statistical comparison of correlation coefficients was reported. Therefore, the current study cannot establish that one biomarker is superior to the other. The study also has limitations. It was a single-center cross-sectional study with 115 participants. NIHSS was assessed at discharge rather than being used solely as a baseline measure. Serial biomarker measurements and longer-term outcomes such as 30- or 90-day modified Rankin Scale were not reported. CRP and ferritin are also nonspecific acute-phase reactants and may be influenced by factors other than cerebral ischemia. Despite these limitations, the parallel increases in CRP and ferritin across NIHSS categories support the potential utility of these biomarkers as adjuncts to conventional neurological assessment.

Admission CRP and serum ferritin concentrations were significantly associated with neurological severity in acute ischemic stroke. Both biomarkers increased progressively from minor to severe NIHSS categories. A strong positive correlation was reported between NIHSS and CRP (r=0.99, p=0.01) and between NIHSS and serum ferritin (r=0.97, p=0.03). These findings suggest that CRP and serum ferritin may serve as readily available adjunctive biomarkers for assessing the severity and prognosis of acute ischemic stroke. However, the present data do not establish independent predictive performance or superiority of one biomarker over the other. Larger prospective multicenter studies incorporating baseline and serial NIHSS assessments, long-term functional outcomes, ROC analysis, and multivariable regression are warranted.