Low levels of serum ionized magnesium are found in patients early after stroke which result in rapid elevation in cytosolic free calcium and spasm in cerebral vascular muscle cells.

Ninety-eight patients admitted to the emergency rooms of three urban hospitals with a diagnosis of either ischemic stroke or hemorrhagic stroke exhibited early and significant deficits in serum ionized Mg2+ (IMg2+), but not total Mg, as measured with a unique Mg2+-sensitive ion-selective electrode. Twenty-five percent of these stroke patients exhibited >65% reductions in the mean serum IMg2+ found in normal healthy human volunteers or patients admitted for minor bruises, cuts or deep lacerations. The stroke patients also demonstrated significant elevation in the serum ionized Ca2+ (ICa2+)/IMg2+ ratio, a sign of increased vascular tone and cerebrovasospasm. Exposure of primary cultured canine cerebral vascular smooth muscle cells to the low concentrations of IMg2+ found in the stroke patients, e.g. 0.30-0.48 mM, resulted in rapid and marked elevations in cytosolic free calcium ions ([Ca2+]i) as measured with the fluorescent probe, fura-2, and digital image analysis. Coincident with the rise in [Ca2+]i, many of the cerebral vascular cells went into spasm. Reintroduction of normal extracellular Mg2+ ion concentrations failed to either lower the [Ca2+]i overload or reverse the rounding-up of the cerebral vascular cells. These results suggest that changes in Mg2+ metabolism play important roles in stroke syndromes and in the etiology of cerebrovasospasm associated with cerebral hemorrhage.

Predictive value of serum ionized but not total magnesium levels in head injuries.

Despite a wealth of recent literature and research on traumatic brain injury, very little has been applicable to diagnosing and treating this syndrome at a tissue level. Part of this problem is the inability to assess rapidly and early in the syndrome the degree or progression of brain injury at a tissue level using simple biochemical analytes. With this in mind, we designed a study in 66 human subjects, who presented with acute blunt head trauma, to determine whether free, ionized serum magnesium (IMg2+) and/or free, ionized serum calcium (ICa2+) levels correlated with the severity of head trauma (HT) and whether any predictive reliable patterns emerge. By using a new ion-selective electrode (ISE) for IMg2+, we have been able to determine IMg2+ and ICa2+ within minutes after sampling in the serum of patients early (1-8 h) after HT. These studies reveal that acute HT is associated with graded deficits (up to 62%, mean = 25%) in serum IMg2+, but not in total serum Mg, which are related to severity of injury based on CT scans and other diagnostic parameters. The greater the degree of injury, the greater the ICa2+/IMg2+ ratio. These ionic findings are compatible with the idea that early ischaemia after head trauma may be important in determining neurological outcome. Our findings provide the first evidence for divalent cation changes in blood after traumatic brain injury, which could be of both diagnostic and prognostic value in patients with traumatic brain injury.