Amino Acid Transmitters in Patients With Headache During the Acute Phase of Cerebrovascular Ischemic Disease

Abstract

Background and Purpose The pathophysiology of headache occurring at stroke onset is unknown. Migraine and ischemia share an excessive release of neuroexcitatory amino acids. Inhibitory amino acids also may be implicated in both diseases. We investigated whether fluctuations of these amino acids occur in headache accompanying cerebral infarction. Methods We studied 100 patients with infarction in the territory of the middle cerebral artery. Neurological impairment was assessed using the Canadian Neurological Scale and Barthel Index. Size of infarction was determined with CT. Twenty-eight patients developed headache. Glutamate, aspartate, and taurine were quantified in blood and cerebrospinal fluid (CSF) within 24 hours of stroke onset with cationic exchange chromatography. Results Stroke subtypes, size of infarct on CT, and clinical scales were similar in patients with and without headache. Plasma glutamate level was 321.14±149.53 μmol/L in patients with headache and 233±107.23 μmol/L in those without headache ( P <.005). Glutamate in CSF was higher in patients with headache (4.6±1.49 μmol/L) than in patients without headache (3.11±1.18 μmol/L) ( P <.001). Aspartate concentrations in plasma and CSF were similar in both groups. Taurine concentrations in plasma were 103.10±52.82 μmol/L and 177.49±90.92 μmol/L in headache and nonheadache patients, respectively ( P <.001). Taurine levels in CSF were 5.42±2.42 μmol/L in patients with headache and 9.27±5.31 μmol/L in those without headache ( P <.001). No significant correlation was found between amino acid levels in plasma or CSF and size of infarction. Conclusions Amino acid neurotransmitters play a role in the pathophysiology of headache that occurs at the onset of stroke. The ischemic penumbral area, more than the infarction itself, may cause a state of cortical hyperexcitability that would be responsible for the cortical release of amino acids and the induction of headache by altering pain perception mechanisms.