Acute cerebral ischemia (ACI), most often manifesting as ischemic stroke, is one of the leading causes of mortality and long-term disability worldwide [1]. Epidemiological studies, such as the INTERSTROKE project, have highlighted that modifiable vascular risk factors— including hypertension, diabetes, smoking, and dyslipidemia—contribute significantly to the global burden of stroke [2].

In India, the incidence of stroke has been estimated to range between 108 and 145 per 100,000 population annually, with metabolic disorders such as hypertension and diabetes being particularly strong contributors [3]. This growing trend highlights the urgent need to identify pathophysiological mechanisms that could serve as therapeutic and prognostic targets.

The pathophysiology of ischemic stroke is complex and multifactorial. A key event is vascular occlusion leading to reduced cerebral perfusion, neuronal ischemia, and the initiation of metabolic cascades that exacerbate injury [4]. Among these, metabolic disturbances such as hyperglycaemia, electrolyte imbalance, and metabolic acidosis have been consistently reported in patients with acute cerebral ischemia and are linked with poor neurological recovery [5]. Hyperglycaemia, for instance, is an independent predictor of increased mortality and disability after stroke, while hyponatremia and elevated lactate levels are associated with worse functional outcomes [6].

In addition to these metabolic changes, neuroinflammation plays a central role in ischemic injury progression. Both innate and adaptive immune responses—including the release of proinflammatory cytokines, leukocyte infiltration, and oxidative stress—amplify neuronal damage and impair recovery [7,8]. Experimental studies also show that T-lymphocyte– mediated neuroinflammation disrupts axonal transport and accelerates neuronal degeneration [9]. These mechanisms not only worsen acute damage but also contribute to long-term cognitive decline and depression after stroke [10].

Furthermore, systemic cardiovascular risk factors significantly modulate stroke onset and recurrence. Atrial fibrillation, hypertension, and dyslipidaemia are among the strongest determinants of ischemic events [11,12]. Recurrence of stroke is multifactorial, with atrial fibrillation, uncontrolled hypertension, and metabolic alterations serving as dominant predictors [13]. Additionally, genetic studies have revealed overlapping polymorphisms between ischemic stroke and cardiovascular disease, suggesting common molecular pathways [14].

Given these complexities, there is increasing recognition that acute ischemic stroke represents the convergence of vascular pathology, metabolic derangements, inflammatory cascades, and genetic susceptibility. Early recognition and correction of metabolic abnormalities may provide an opportunity to improve neurological outcomes. This study therefore prospectively evaluates the spectrum of metabolic alterations in ACI patients and explores their correlation with short-term clinical outcomes.

Aims and Objectives

Aim:

To study the prevalence and clinical impact of metabolic alterations in patients with acute cerebral ischemia.

Objectives:

1. To identify the common metabolic abnormalities (blood glucose, sodium, potassium, calcium, lactate, lipid profile, renal markers, and ABG parameters) in ACI patients.
2. To correlate these metabolic parameters with stroke severity using the NIH Stroke Scale (NIHSS).
3. To assess their association with functional outcomes at 30 days using the modified Rankin Scale (mRS).
4. To explore the role of inflammation and dyslipidaemia in predicting poor

Study Design and Setting

• Prospective observational study conducted at Chandramma Dayanand Sagar Institute of Medical Education and Research.
• Duration: October 2023 – June 2025. Study Population
• Sample size: 250

·       Inclusion criteria:

• Adults (>18 years) with acute ischemic stroke confirmed by clinical evaluation and neuroimaging (CT/MRI).
• Stroke onset within 24

·       Exclusion criteria:

• Haemorrhagic
• Chronic kidney/liver
• Pre-existing metabolic disorders unrelated to acute stroke (e.g., inborn errors of metabolism).

Data Collection

• Demographic and clinical data: age, sex, comorbidities (HTN, DM, AF, dyslipidaemia, prior stroke).
• Neurological assessment: NIHSS at admission and 30 days; functional outcome by mRS at 30 days.

·       Laboratory investigations within 24 hours of admission:

• Blood glucose,
• Serum electrolytes (Na⁺, K⁺, Ca²⁺).
• Serum urea, creatinine, uric
• Arterial blood gases (ABG) – pH, HCO₃⁻,
• Lipid profile (total cholesterol, LDL, HDL, triglycerides).
• Inflammatory markers: leukocyte count,

Outcomes

• Primary outcome: Association of metabolic alterations with poor functional outcome (mRS ≥ 3 at 30 days).
• Secondary outcome: Relationship between metabolic derangements and stroke severity (NIHSS).

Statistical Analysis

• Performed using SPSS v25. Descriptive statistics: mean ± SD, frequencies (%). Chi-square and t-tests for categorical and continuous Logistic regression for predictors of poor outcomes. Significance level: p < 0.05.

Baseline Demographic and Clinical Characteristics

A total of 250 patients with acute cerebral ischemia were included. The mean age was 64.5 ± 10.8 years, with a male-to-female ratio of 59%:41%. Hypertension was the most common comorbidity (68.8%), followed by diabetes mellitus (55.2%) and dyslipidaemia (37.6%). Atrial fibrillation was present in 15.2%, while 11.6% had a previous history of stroke or transient

ischemic attack (TIA). The mean NIHSS score at admission was 12.4 ± 5.6, reflecting moderate-to-severe neurological deficits.

Table 1. Baseline Demographic and Clinical Characteristics (n = 250)

Metabolic Alterations Observed

Significant metabolic abnormalities were identified in the majority of patients. Hyperglycaemia was the most frequent alteration, seen in 65%, followed by hyponatremia (42%) and dyslipidaemia (45.6%). Elevated serum lactate (38%) and metabolic acidosis (24.8%) were observed in a considerable proportion of patients, indicating impaired metabolic homeostasis. Inflammatory markers were frequently abnormal, with leucocytosis (40.4%) and elevated ESR (48.8%) suggesting a high prevalence of systemic inflammation.

Table 2. Metabolic Alterations Observed

Association of Metabolic Abnormalities with Outcomes

At 30-day follow-up, outcomes were assessed using the modified Rankin Scale (mRS). Patients with poor outcomes (mRS ≥3) were more likely to have hyperglycaemia (74%, p<0.01), hyponatremia (58%, p <0.05), elevated lactate (69%, p <0.01), and metabolic acidosis (71%, p <0.01). Dyslipidaemia showed a non-significant trend toward poorer outcomes (52%, p = 0.06). Inflammatory markers were also associated, with leucocytosis predicting worse

prognosis (65%, p <0.05).

Table 3. Association of Metabolic Abnormalities with Outcomes (mRS ≥3 at 30 days)

NS = not significant; * = significant; ** = highly significant

The present study evaluated the prevalence of metabolic alterations in patients with acute cerebral ischemia (ACI) and their association with short-term clinical outcomes. Our results demonstrate that metabolic disturbances such as hyperglycaemia, hyponatremia, dyslipidaemia, elevated lactate, metabolic acidosis, and systemic inflammatory markers are highly prevalent in stroke patients. Importantly, several of these abnormalities, including hyperglycaemia, hyponatremia, elevated lactate, metabolic acidosis, and leucocytosis, were strongly associated with poor functional outcomes at 30 days. These findings emphasize the importance of recognizing and correcting metabolic derangements early in the course of acute stroke management.

Comparison with Global Burden and Indian Data

Stroke remains a major cause of disability and mortality worldwide, ranking as the second leading cause of death and a primary driver of long-term disability [1]. In India, the burden is rising, with incidence rates ranging from 108 to 145 per 100,000 population annually, largely fuelled by uncontrolled hypertension, diabetes, and dyslipidaemia [2]. Large multicentre studies such as the INTERSTROKE trial have consistently highlighted hypertension, diabetes, dyslipidaemia, smoking, and atrial fibrillation as dominant risk factors [3]. Our cohort reflects these patterns, with nearly 70% hypertensive and 55% diabetic, reinforcing the significance of vascular risk factors in this population.

Hyperglycaemia and Clinical Outcomes

In our study, hyperglycaemia was the most common metabolic abnormality (65%), and it correlated strongly with poor outcomes (74% with mRS ≥3, p <0.01). Hyperglycaemia at admission is well recognized as a predictor of infarct expansion, haemorrhagic transformation, and poor recovery [21]. Mechanistically, elevated glucose enhances lactic acidosis in ischemic tissue, worsens oxidative stress, and promotes excitotoxicity, thereby exacerbating neuronal damage [24]. Prior studies confirm that even in non-diabetic patients, stress-induced hyperglycaemia is associated with adverse outcomes [21]. These findings reinforce the need for stringent glucose monitoring and management in stroke units.

Electrolyte Abnormalities: Hyponatremia and Hypocalcaemia

Electrolyte disturbances were frequent in our cohort. Hyponatremia occurred in 42% of patients and was significantly associated with poor outcomes (58%, p <0.05). Similar to previous studies, hyponatremia may result from cerebral salt-wasting syndrome or syndrome of inappropriate antidiuretic hormone secretion (SIADH) following stroke [11]. Both mechanisms lead to cerebral edema and worsen neurological deficits. Correction of sodium imbalance, therefore, remains a crucial supportive measure.

Hypocalcaemia, observed in 18.8% of our patients, although not directly linked with poor short-term outcomes, has been shown in earlier Indian studies to be a poor prognostic marker in ischemic stroke [12]. Calcium plays an essential role in neuronal signaling, and its depletion exacerbates excitotoxic injury. Larger prospective studies are warranted to clarify this relationship further.

Elevated Lactate and Metabolic Acidosis

Elevated serum lactate (38%) and metabolic acidosis (25%) were observed in a significant proportion of our patients, and both abnormalities were strongly associated with poor outcomes (69% and 71%, respectively). Tissue hypoxia and anaerobic glycolysis contribute to lactic acid accumulation, reflecting the severity of cerebral ischemia [24]. Metabolic acidosis, in turn, aggravates neuronal dysfunction and impairs the efficacy of neuroprotective interventions. These findings suggest that serum lactate could serve as a bedside biomarker of stroke severity and prognosis, complementing traditional clinical scoring systems.

Dyslipidaemia and Uric Acid

Dyslipidaemia was present in 45.6% of patients, though its association with poor outcomes did not reach statistical significance (p = 0.06). Lipid abnormalities are a well-known risk factor for stroke [9], and long-term studies confirm the protective role of statins in reducing recurrence and mortality [18]. However, in the acute phase, lipid levels may not directly predict short-term functional recovery, which explains our findings.

Elevated uric acid levels were detected in 35% of patients. While uric acid has paradoxical roles—as both a pro-oxidant and an antioxidant—its clinical significance in acute stroke remains debated. Some studies suggest protective antioxidant effects, while others associate hyperuricemia with poor vascular outcomes [20]. This dual role underscores the need for mechanistic studies in diverse populations.

Systemic Inflammation and Stroke Outcomes

Inflammatory markers were highly prevalent, with 40.4% leucocytosis and 48.8% elevated ESR. Both were significantly associated with worse outcomes. Stroke triggers an intense inflammatory response involving cytokine release, oxidative stress, and immune cell infiltration [13,14]. Experimental and clinical studies consistently show that neuroinflammation amplifies ischemic injury and worsens prognosis [22,23]. Leucocytosis, in particular, may reflect systemic inflammation and stress response, and its association with mortality and disability has been reported in multiple cohorts [15,16]. Anti-inflammatory strategies remain an exciting target for future stroke therapies.

Genetic and Cardiovascular Risk Interactions

Beyond metabolic derangements, genetic predisposition plays a crucial role in stroke risk. Genome-wide association studies have identified several loci shared between stroke and cardiovascular disease [4,5]. The interaction of these genetic markers with metabolic and lifestyle risk factors (hypertension, obesity, dyslipidaemia) explains the heterogeneity in stroke presentations and outcomes [7,10]. Our findings of a high prevalence of metabolic abnormalities further highlight the interplay between genetics, vascular risk, and acute metabolic responses in shaping recovery trajectories.

Clinical Implications

The recognition of metabolic abnormalities in stroke care has significant implications for acute management and rehabilitation. Hyperglycaemia and electrolyte disturbances are modifiable with timely intervention. Lactate monitoring may provide a rapid bedside tool for risk stratification. Incorporating metabolic panels into stroke protocols could enhance prognostic accuracy and guide personalized care. In resource-limited settings such as India, where stroke burden is high and critical care resources scarce [2], cost-effective metabolic monitoring could improve outcomes significantly.

Limitations

This study has certain limitations. Being a single-centre cross-sectional study, causality cannot be firmly established. The sample size, though adequate, may not capture the full heterogeneity of Indian stroke populations. We also assessed only short-term outcomes (30 days), whereas long-term disability and mortality trends may differ. Despite these limitations, the study provides robust evidence linking metabolic disturbances with poor functional outcomes and underscores the need for early correction strategies.

Future Directions

Future research should focus on prospective, multicentre studies with larger cohorts to validate these findings. Incorporating advanced biomarkers of oxidative stress and inflammation could further elucidate mechanistic pathways [13,14,20]. Trials testing targeted correction of glucose, sodium, and acid-base disturbances in acute stroke are warranted. Moreover, integrating genetic and metabolic profiling may allow for personalized risk prediction and intervention strategies [5,7,19].

In summary, our study highlights that metabolic abnormalities are highly prevalent in acute ischemic stroke and strongly associated with poor functional outcomes. Hyperglycaemia, hyponatremia, elevated lactate, metabolic acidosis, and leucocytosis emerge as key prognostic markers. Early recognition and correction of these derangements should form an integral part of comprehensive stroke care, especially in high-burden regions such as India.

These findings align with global evidence and offer a pragmatic approach to improving outcomes in acute stroke management.

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