What are the temporal trends in metabolomics (study of small molecule metabolites) profiles of patients with acute ischemic stroke?

Temporal Trends in Metabolomics Profile of Acute Ischemic Stroke

Recent metabolomic studies (2020-2024) have identified distinct temporal patterns in metabolite profiles of acute ischemic stroke patients, with significant differences between acute and chronic phases that can aid in diagnosis, prognosis, and understanding of stroke pathophysiology.

Key Metabolite Changes in Acute Ischemic Stroke

Acute Phase Metabolite Alterations

• Elevated levels of lactate, carbonate, and glutamate are observed in the acute phase of ischemic stroke, reflecting energy deficit and excitotoxicity 1
• Decreased levels of multiple amino acids including alanine, glycine, isoleucine, leucine, serine, tyrosine, methionine, and tryptophan are characteristic of the acute phase 1, 2
• Ketones, branched-chain amino acids (BCAAs), and inflammatory compounds are typically elevated in the acute phase, while alanine and glutamine are decreased 2
• Tyrosine, lactate, and tryptophan form a panel of potential biomarkers that can diagnose acute ischemic stroke with high precision (91.7%) 1

Chronic Phase Metabolite Changes

• Many acute phase metabolites return to normal levels in the chronic phase, particularly ketones, BCAAs, and inflammatory markers 2
• Certain lipid metabolites, including fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins, remain altered in both acute and chronic phases compared to controls 2
• The transition from acute to chronic phase shows normalization of many energy metabolism and amino acid-related markers 2

Stroke Subtype-Specific Metabolomic Profiles

• Different stroke subtypes (large-artery atherosclerosis vs. cardioembolic vs. small artery occlusion) demonstrate distinct metabolomic signatures 3, 4
• Six key metabolites (lysine, serine, threonine, kynurenine, putrescine, and lysophosphatidylcholine acyl C16:0) can discriminate between large-artery atherosclerosis and cardioembolic stroke 3
• Small artery occlusion can be distinguished from large-artery atherosclerosis by differences in L-pipecolic acid, 1-Methylhistidine, phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LysoPE), and lysophosphatidylcholine (LysoPC) 4
• These subtype-specific metabolites affect distinct pathways including glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, histidine metabolism, and lysine degradation 4

Pathophysiological Pathways Reflected in Metabolite Changes

• Disturbed amino acid metabolism is a prominent feature in acute ischemic stroke, with most dysregulated metabolites closely correlated with each other 1
• Fatty acid metabolism alterations are evident in the acute phase, with changes in oleic acid, linoleic acid, and arachidonic acid 4
• Metabolite changes reflect key pathophysiological processes including inflammation, energy deficit, oxidative stress, neurotoxicity, neuroexcitation, and neuronal injury 1, 5
• Osmolality changes are important to monitor, as elevated osmolality (>295 mOsm/kg) during the initial 7 days of acute stroke is associated with increased mortality within 3 months 6

Clinical Applications and Future Directions

• Metabolomic profiles can potentially improve early diagnosis of stroke, with specific metabolite panels achieving high diagnostic accuracy 1, 3
• Targeted metabolomics may enhance diagnostic yield for stroke subtypes, potentially reducing the need for extensive and costly diagnostic workups 3
• Monitoring metabolite changes over time can provide insights into stroke progression and recovery 2
• Future research should explore the pathophysiological pathways of identified metabolites to develop novel therapeutic approaches 3, 5
• Proper hydration management based on osmolality monitoring is essential, with the American Stroke Association recommending maintenance intravenous fluids at approximately 30 mL per kilogram of body weight daily for euvolemic patients 6

Methodological Considerations in Metabolomic Studies

• Most clinical studies use biofluids (blood or plasma) collected within 3 days of symptom onset for metabolomic analysis 3, 5
• Various analytical platforms are used, including gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy 1, 4, 2
• Sample sizes in recent studies range from 40-346 stroke patients, with varying numbers of control subjects 1, 3, 2
• Longitudinal study designs comparing acute and chronic phases provide more comprehensive insights than case-control studies alone 2